The present invention relates to the use of a particular class of aromatic compounds, in particular bis-aromatic xcex1,xcex2-unsaturated ketones, most of which are novel compounds, for the treatment or prophylaxis of a number of serious conditions caused by microorganisms or parasites, in particular protozoa such as Leishmania, Plasmodia, and Coccidia such as Eimeria, and intracellular bacteria, including Legionella and Mycobacteria. The invention also relates to the novel bis-aromatic xcex1,xcex2-unsaturated ketones and methods of preparing them, as well as to pharmaceutical and antiparasitic compositions. Furthermore, the invention also relates to a method for treatment or prophylaxis of diseases caused by microorganisms or parasites.
Parasitic diseases, among these malaria and leishmaniasis, are, on a world basis, among the most important diseases. The most effective known drugs against the diseases have many side effects for which reason it is not possible to maintain the treatment or prophylaxis of specific diseases for years.
Recently, the development of resistance against the available drugs against particularly malaria and leishmania parasites has been reported.
Especially malaria and leishmaniasis remain serious diseases despite the efforts to control the diseases and reduce their prevalence by vector eradication and drug treatment.
More than 12 million people in the world are inflicted by leishmaniasis. There are more than 400,000 new cases and 100,000 deaths each year but as many as 350 million people are at risk of infection (WHO,1990). The annual incidence of clinical leishmaniasis is estimated to exceed 2,000,000 cases in some 80 countries. It is one of the 7 important tropical diseases included in the TDR program.
Leishmaniasis are characterized by a broad spectrum of clinical manifestations depending on the strain of the parasite and the host immune response. The parasites infect macrophages and multiply inside these cells. The first step in the Leishmania/macrophage interactions is the binding of the parasite to the macrophage followed by uptake of the parasite. Integrity and fluidity of the host cell membrane is essential for this interaction. Certain parasite surface antigens such as membrane glycoprotein (Gp63) and lipophosphoglycan (LPG) as well as a number of macrophage surface receptors are also important in binding and uptake of the parasite by macrophages.
Various species of the protozoan parasite Leishmania cause a broad spectrum of diseases ranging from the cutaneous healing skin lesions caused by L. major to a fatal visceral form of the disease called kala azar caused by L. donovani (Manson-Bahr, 1987). Leishmaniases are widespread in many parts of the world with highest prevalence in Africa, Asia, and Latin America (WHO, 1989). Recently an increasing number of AIDS patients are becoming infected with Leishmania (Brenguer, 1989; Flegg 1990).
Therapy of patients with leishmaniasis still poses a serious problem. Most of the available antileishmanial drugs exhibit considerable toxicity and there are reports of large scale clinical resistance to the conventional antimonial drugs. No effective, safe, and nontoxic antileishmanial drug is available at present.
There are also reports of large scale clinical drug resistance in visceral leishmaniasis. (TDR News No. 34, 1990)
Malaria, another parasitic disease, is also a serious health problem. Human malaria is caused by four species of the protozoan genus, Plasmodium. The species Plasmodium falciparum is the most dangerous, causing acute severe infections that are often fatal, especially in young children and immigrants entering endemic areas. The life cycle of P. falciparum includes different stages; in the first stage, the sporozoite stage, the parasite is brought into the blood stream by the Anopheles mosquito. The sporozoites are carried in the blood stream to the liver where they invade the hepatocytes and develop into merozoites in the course of 5-7 days. Merozoites released from infected cells start a new cycle by invading the erythrocytes. It is the invasion of the erythrocyte which gives rise to the clinical disease. In the erythrocyte, the parasite shows an asexual multiplication which involve a maturation of the parasite through different parasite stages, the ring, the trophozoite and the schizont stage (the stage that undergoes nuclear division). When the schizont-infected erythrocyte bursts, new merozoites are released. Some merozoites, however, differentiate into gametocytes (microgametocytes and macrogametocytes), the sexual form of the parasite. Contrary to the asexual infected erythrocytes, these sexual parasite stages are able to continue the life cycle when the infected cells, the erythrocytes, are ingested by mosquitoes during a blood meal. By fertilization in the mosquito gut, the gametocytes develop into a mobile ookinete stage. The ookinete pass through the epithe and matures into a oocyst. In the oocyst, the new sporozoites develop. These sporozoites are released and move to the salivary gland, and are then ready to be injected into a new host. The parasites are haploid in most of the life cycle as they perform a meiotic cell division shortly after fertilization. The Anopheles mosquito is the primary vector of malaria, but the disease can be seen after blood transfusion, i.v. injection of medicaments and after transfer from an infected mother to the newborn child through the placenta.
Each year, several hundreds of millions of human beings are affected by the parasitic disease malaria. The treatment and prophylaxis of malaria has been difficult because the available drugs exhibit severe side effects, and furthermore, the Plasmodia are showing increasing resistance towards the drugs (Ann (WHO) 1990).
Coccidial protozoa such as Eimeria tenella are some of the most important parasites causing disease in poultry resulting in significant economic loss. There are problems with resistance development against some of the available anticoccidial drugs used in prophylaxis and treatment of these diseases, for which reason there is a need for development of new anticoccidial drugs.
Also, Babesia species cause devastating damage to cattle in many parts of the world, and there is a need for the development of safe, effective and inexpensive drugs to control these diseases.
Thus, there is a great need for effective drugs against parasitic diseases, especially for drugs exhibiting none or only less severe side effects.
According to the present invention, it has been found that a class of aromatic compounds, said class comprising compounds containing an alkylating site, show a remarkable capability of effectively suppressing the growth of parasitic protozoa and intracellular bacteria, which compounds at the same time can be so chosen that they are tolerable to animal cells such as human cells. This valuable selective activity of such alkylating aromatic compounds seems to be based on their capability of interfering with oxygen metabolism in the parasites by destroying their mitochondria, at concentrations at which the compounds, while thus being harmful to the microorganisms, do not affect the mitochondria of the animal cells.
Without being limited to any particular theory, it is believed that the capability of the compounds to alkylate nucleophilic groups in biomolecules, as evidenced by their capability of alkylating the thiol group of N-acetyl-L-cysteine, is of importance for the antimicrobial effect.
In accordance with this, the present invention, in its broadest aspect, relates to the use of an aromatic compound which contains an alkylating site, and which is capable of alkylating the thiol group in N-acetyl-L-cysteine at physiological pH, for the preparation of a pharmaceutical composition or a medicated feed, food or drinking water for the treatment or prophylaxis of a disease caused by a microorganism or a parasite in an animal, including a vertebrate, such as a bird, a fish or a mammal, including a human, the microorganism or parasite being selected from
parasitic protozoa, in particular tissue and blood protozoa such as Leishmania, Trypanosoma, Toxoplasma, Plasmodium, Pneumocystis, Babesia and Theileria; intestinal protozoan flagellates such as Trichomonas and Giardia; intestinal protozoan Coccidia such as Eimeria, Isospora, Cryptosporidium; Cappilaria, Microsporidium, Sarcocystis, Trichodina, Trichodinella, Dacthylogurus, Pseudodactylogurus, Acantocephalus, Ichthyophtherius, Botrecephalus; and intracellular bacteria, in particular Mycobacterium, Legionella species, Listeria, and Salmonella.
As it will appear from the following, the aromatic compound may in many cases advantageously be used in the form of a prodrug of the aromatic compound, and it will be understood that the present broadest aspect of the invention encompasses the use of such prodrugs. Expressed in another manner, the broadest aspect of the invention relates to a method for the treatment or prophylaxis of a disease caused by a microorganism or a parasite selected from the protozoa and bacteria stated above, the method comprising administering, to an animal in need thereof, an effective amount of an aromatic compound which contains an alkylating site, and which is capable of alkylating the thiol group in N-acetyl-L-cysteine at physiological pH, or a prodrug thereof.
From the description which follows, it will be seen that a large number of aromatic compounds which show the above-mentioned selective effect are compounds which have one or several electrondonating groups such as hydroxy or derivatives thereof substituted on an aromatic ring. It is believed that the above-described selectivity is obtained through such adequate substitution which modifies the alkylating potency. It will also appear from data described herein that important representatives of the compounds in question are compounds which contain an aromatic ring attached to the alkylating site.
As appears from the following, convenient and reproducible in vitro tests have been devised to test the selectivity of aromatic N-acetyl-L-cysteine-thiol-alkylating compounds, and based on a large number of tested compounds, it has been found that the above-mentioned aromatic N-acetyl-L-cysteine-thiol-alkylating compounds in which one or several electron-donating groups such as hydroxy or derivatives thereof is/are present on an aromatic ring, are almost consistently capable of showing a useful selectivity, resulting in effective suppression of the growth of pathogenic microorganisms or parasites in concentrations which are well tolerated by animal cells.
The in vitro tests involve establishing the inhibition of the multiplication of the protozoa or bacteria on the one hand and the animal cells on the other hand by determining the inhibition of the uptake of radiolabelled precursors as an indication of the inhibition of the growth of the parasite or the animal cells in the presence of the test compound in the concentration in question (see Example 14 herein and the examples to which it refers).
The tests involve a particularly suitable assay for assessing the tolerability of the aromatic alkylating compounds to animal cells, that is, an assay based on the assessment of the reduction caused by the compound on the thymidine uptake by lymphocytes of the animal in the Lymphocyte Proliferation Assay (LPA) which is the assay described in greater detail in Example 13.
It has also been found that compounds which are found to be promising in the in vitro model also cure animals infected with leishmania and malaria parasites, respectively, such as was shown in a suitable model involving intraperitoneal administration of the compounds to mice or hamsters (see Examples 8, 9 and 16).
Furthermore, it has been found that compounds with antileishmanial and antimalarial activity exhibit inhibitory effect on the growth of intracellular bacteria such as Mycobacteria which causes tuberculosis in humans, and Legionella which causes legionnaires disease in humans (see Examples 17 and 19).
The fact that these compounds exhibit strong antiparasitic activity against several species of two important human protozoan parasites, Plasmodium and Leishmania, and against Eimeria tenella, the most important parasite in poultry (see Example 28) makes it justified to presume that these compounds will also be strongly active against important veterinarian protozoan parasites such as Babesia in cattle, which is intraerythrocytic similar to the malaria parasite, other Coccidia in poultry, and Pseudodactylogurus or Trichodina in fish.
Furthermore, based on the broad spectrum antimicrobial activity of the compounds (see Examples, 17, 18 and 19), it can be assumed that these compounds have similar activity against other microorganisms such as Salmonella, and Trichinella, and quite generally against a broad range of microorganisms as defined below, in particular aerobic microorganisms and, among those, in particular microorganisms which are found in tissues and host cells of an infected animal.
While it has been established that the alkylating site may be a carbon-carbon double bond conjugated with a carbonyl group, it is contemplated, based on general chemical considerations, that it may also be a carbon-carbon triple bond conjugated with a carbonyl group, or an epoxy group. It is preferred that the alkylating site is a double or triple bond (from the point of view of availability of the compound preferably a double bond) conjugated with a carbonyl group. The carbonyl group may be the carbonyl group of an aldehyde or a ketone, or it may be the Cxe2x95x90O group of a carboxylic acid group or a derivative thereof such as an ester.
In a preferred class of compounds, the carbonyl group is a ketonic carbonyl group which is further conjugated with an aromatic ring, such as a phenyl group. In this case, the phenyl group may carry electron-donating groups, confer what is discussed above, in particular one or several hydroxy groups or derivatives thereof. In the case of hydroxy groups, these may be masked in order to prevent metabolism, confer the detailed discussion further below. The masking groups are preferably chosen from groups from which the free phenol may be released in the body, either enzymatically or non-enzymatically.
Considering that human lymphocytes are representatives of sensitive animal cells, it is, as a general rule, it is preferred according to the present invention that the aromatic alkylating compound is one which, in a concentration in which it causes less than 50% reduction, preferably less than 40% reduction, and more preferably less than 20% reduction, of the thymidine uptake by human lymphocytes in the Lymphocyte Proliferation Assay using phytohemagglutinin (PHA), meets at least one of the following criteria:
a) the aromatic compound is capable of inhibiting in vitro the growth or multiplication of Leishmania major promastigotes by at least 80%, as determined by uptake of tritiated thymidine,
b) the aromatic compound is capable of inhibiting in vitro the growth or multiplication of Plasmodium falciparum by at least 80%, as determined by uptake of tritiated hypoxanthine,
c) the aromatic compound is capable of inhibiting in vitro the growth or multiplication of Eimeria tenella in chicken fibroblast cell cultures by at least 70%, as determined by counting the parasites,
d) the aromatic compound is capable of inhibiting in vitro the growth or multiplication of Mycobacterium tuberculosis or Legionella pneumophila by at least 50%, as determined by colony counts.
However, it will be understood that the most important consideration is that the compound is tolerable to the animal in concentrations in which it will control the protozoa or the intracellular bacteria. In particular, preferred compounds to be used according to the invention are compounds which meets all of the criteria a) to d), because this is an indication of a broad-spectred activity and selectivity.
According to an embodiment of the use according to the present invention, the pharmaceutical composition prepared is a composition for the treatment or prophylaxis of diseases caused by Leishmania in humans or dogs, and the aromatic compound used is capable of inhibiting in vitro the growth of Leishmania major promastigotes by at least 80%, as determined by uptake of tritiated thymidine, in a concentration of the compound in which it causes less than 50% reduction, preferably less than 40% reduction, more preferably less than 20% reduction, of the thymidine uptake by human lymphocytes in the Lymphocyte Proliferation Assay using PHA.
In the following, reasonable selection criteria based upon the behaviour of the compounds in representative tests are stated for compounds to be used for treatment or prophylaxis of a number of diseases, confer the corresponding claims 10-24:
As determined by a representative in vivo test, the pharmaceutical composition for the treatment or prophylaxis of diseases caused by Leishmania in humans or dogs, is preferably one in which the aromatic compound, or the prodrug, when administered intraperitoneally in the in vivo test described in Example 8 herein in a dose of up to 20 mg per kg body weight, especially in a dose of up to 10 mg er kg body weight, once daily for 40 days to female BALB/c mice which have been infected with L. major (107/mouse), the administration being initiated one week after infection, is capable of preventing increase in lesion size by at least 60%, preferably at least 80%, more preferably at least 90%.
In another embodiment, the pharmaceutical composition is a composition for the treatment or prophylaxis of diseases caused by Leishmania in humans or dogs, and the aromatic compound, or the prodrug, when administered intraperitoneally in the in vivo test described in Example 9 herein in a dose of up to 20 mg per kg body weight, preferably in a dose of up to 10 mg per kg body weight, two times daily for 7 days to male Syrian golden hamsters which have been infected with L. donovani promastigotes (2xc3x97107/hamster), the administration being initiated one day after infection, is capable of reducing the parasite load in the liver of the hamsters by at least 60%, preferably by at least 80%, and more preferably by at least 90%.
In yet another embodiment, the pharmaceutical composition is a composition for the treatment or prophylaxis of malaria caused by Plasmodium spp. in humans, and the aromatic compound is capable of inhibiting in vitro the growth of Plasmodium falciparum by at least 80%, as measured by uptake of tritiated hypoxantine, in a concentration of the compound in which it causes less than 50% reduction, preferably 40% reduction, more preferably 20% reduction, of the thymidine uptake by human lymphocytes, as measured by the Lymphocyte Proliferation Assay using PHA.
In yet a further embodiment, the pharmaceutical composition is a composition for the treatment or prophylaxis of diseases caused by Plasmodium spp. in humans, and the aromatic compound, when administered intraperitoneally in the in vivo test described in Example 16 herein in a dose of up to 20 mg per kg body weight two times daily for 6 days to female BALB/c mice which have been infected with malaria P. yoelii (2xc3x97105/mouse), the administration being initiated one day after infection, is able to prevent increase in the parasitemia during the administration period. In particular, the aromatic compound, or the prodrug, when administered intraperitoneally in the in vivo test described in Example 16 herein in a dose of up to 20 mg per kg body weight two times daily for 10 days to 8 weeks old female BALB/c mice which have been infected with malaria P. yoelii (2xc3x97105/mouse), the administration being initiated one day after infection, is capable of clearing the parasite from the mice within at the most 23 days.
Especially, the aromatic compound, or the prodrug, when administered intraperitoneally in the in vivo test described in Example 16 herein in a dose of up to 20 mg per kg body weight two times daily for 8 days to 8 weeks old female BALB/c mice which have been infected with malaria P. yoelii strain YM (1xc3x97106/mouse), the administration being initiated one day after infection, is capable of clearing the parasite from the mice within at the most 21 days, preferably within at the most 17 days.
It is also preferred that the aromatic compound, or the prodrug, when administered intraperitoneally in the in vivo test described in Example 16 herein in a dose of 5 mg per kg body weight two times daily for 10 days to 8 weeks old female BALB/c mice which have been infected with malaria P. yoelii (2xc3x97105/mouse), the administration being initiated one day after infection, is capable of clearing the parasite from the mice within at the most 23 days. In particular, the aromatic compound, or the prodrug, when administered intraperitoneally in the in vivo test described in Example 16 herein in a dose of 5 mg per kg body weight two times daily for 8 days to 8 weeks old female BALB/c mice which have been infected with malaria P. yoelii strain YM (1xc3x97106/mouse), the administration being initiated one day after infection, is capable of clearing the parasite from the mice within at the most 21 days, preferably within at the most 17 days.
In a further embodiment of the invention, use is made of an aromatic compound, or a prodrug thereof, which aromatic compound contains an alkylating site and which aromatic compound is capable of alkylating the thiol group in N-acetyl-L-cysteine at physiological pH, for the preparation of a pharmaceutical composition or a medicated feed or drinking water for the treatment or propylaxis of diseases caused by Coccidia in poultry such as chickens or turkeys, wherein the aromatic compound, or the prodrug, when administered to chickens with the feed in a concentration of up to 400 ppm for at most 28 days in the in vivo test described in Example 28 herein, is capable of controlling infection by Eimeria tenella in at least 60% of the chickens and preventing pathological alterations in at least 50% of the chickens, the aromatic compound preferably being one which in a concentration of up to 120 ppm for at most 28 days in the in vivo test described in Example 28 herein, is capable of controlling infection by Eimeria tenella in at least 60% of the chickens and preventing pathological alterations in at least 65% of the chickens.
In a further embodiment, the pharmaceutical composition is a composition for the treatment or prophylaxis of diseases caused by intracellular bacteria such as Mycobacteria in humans or animals such as cattle, and the aromatic compound is one which is capable of inhibiting the growth and multiplication of Mycobacteria tuberculosis or Legionella pneumophila in vitro in the test described in Example 17 herein at a mean MIC of 10 xcexcg per ml, and, in the same concentration, causes less than 50% reduction of the thymidine uptake of human lymphocytes as measured by The Lympocyte Proliferation Assay.
The aromatic compound is preferably one which contains an aromatic ring attached to the alkylating site. As indicated above, the compound in particular one which has electron-donating groups attached to an aromatic ring.
In the aromatic compound, the alkylating site is typically a double or triple bond conjugated with a carbonyl group which carbonyl group optionally is further conjugated with an aromatic ring such as a phenyl group, the aromatic ring attached to the alkylating site preferably containing at least one electron-donating group such as an oxygen, nitrogen or sulphur function such as hydroxy, alkoxy (e.g. methoxy), amino, alkylamino, dialkylamino, mercapto, or alkylthio. It is preferred that the electron-donating group(s) is/are attached to the aromatic ring in a position next to and/or most remote relative to the position through which the aromatic ring is attached to the alkylating site.
Particularly important diseases to be treated or prevented by means of the composition prepared according to the invention are human leishmaniasis caused by Leishmania donovani, L. infantum, L. aethiopica, L. major, L. tropica, L. mexicana complex, or L. braziliensis complex or human malaria caused by Plasmodium falciparum, P. ovale, P. vivax, or P. malariae, as well as parasitic diseases in livestock, such as Babesia in cattle, or a parasitic disease in birds, such as a disease caused by Coccidia such as Eimeria tenella in poultry such as chicken or turkey, or a parasitic disease in fish, such as Pseudodactylogurus or Trichodina.
The important human malaria parasites with which hundreds of millions of humans are infected, are Plasmodium falciparum, P. ovale, P. vivax, and P. malariae. In particular, Plasmodium falciparum is the most important human parasite and the number one parasite killer of mankind. The malaria parasites show widespread resistance against almost all available antimalarial drugs. For this reason, the fact that a new class of antimalarial drugs, chemically unrelated to the known antimalarial drugs has been provided, is a feature of the invention which is of great importance. Another important aspect of the invention is that malaria parasites resistant against Chloroquine, the most commonly used antimalarial drug, show very high degree susceptibility to the compounds described herein (Example 15).
Another important aspect of the invention is the antileishmanial activity of the compounds defined above. Visceral leishmaniasis, caused by Leishmania donovani or L. infantum, inflicts several million people in the world, and this disease recently appears to be a major problem for AIDS patients coming in contact with Leishmania parasites, combined with large scale clinical resistance in endemic areas such as India (which is announced xe2x80x9calarmingxe2x80x9d by the World Health Organization). Other major diseases are diseases caused by other species of Leishmania, such as L. aethiopica, L. major, L. tropica, L. mexicana complex, and L. braziliensis complex. Some of these species cause severe disfiguring and morbidity in millions of humans in Central and South America and many parts of Africa.
In one preferred aspect, the invention relates to the use of an aromatic compound which is a bis-aromatic xcex1,xcex2-unsaturated ketone of the general formula I
Xmxe2x80x94Ar1xe2x80x94COxe2x80x94Wxe2x80x94Ar2xe2x80x94Ynxe2x80x83xe2x80x83I
wherein
W is eitherxe2x80x94CRxe2x95x90CRxe2x80x94 or xe2x80x94Cxe2x89xa1Cxe2x80x94, wherein each R independently of the other R designates hydrogen, C1-3 alkyl, or halogen,
Ar1 and Ar2 are the same or different and each designate an aromate selected from phenyl and 5- or 6-membered unsaturated heterocyclic rings containing one, two or three heteroatoms selected from oxygen, sulfur, and nitrogen, such as furanyl, thiophenyl, pyrrolyl, indazolyl, isoxazolyl, oxazolyl, thiazolyl, pyrazolyl, pyridinyl, or pyrimidinyl, which aromate may be substituted with one or more substituents selected from
halogen; nitro; nitroso; and C1-12, preferably C1-6, straight or branched aliphatic hydrocarbyl which may be saturated or may contain one or more unsaturated bonds selected from double bonds and triple bonds, which hydrocarbyl may be substituted with one or more substituents selected from hydroxy, halogen, amino, and amino which is optionally alkylated with one or two C1-6 alkyl groups;
Y and X are the same or different and each designate a group ARH or a group AZ, wherein A is xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, or xe2x80x94N(C1-6 alkyl)-, RH designates C1-6 straight or branched aliphatic hydrocarbyl which may be saturated or may contain one or more unsaturated bonds selected from double bonds and triple bonds, and Z designates H or (when the compound is a prodrug) a masking group which is readily decomposed under conditions prevailing in the animal body to liberate a group AH, in which A is as defined above; m designates 0, 1 or 2, and n designates 0, 1, 2 or 3, whereby, when m is 2, then the two groups X are the same or different, and when n is 2 or 3, then the two or three groups Y are the same or different, with the proviso that not both of n and m are 0.
When Z designates a masking group, it may typically be selected from the below groups (A)-(E)
xe2x80x94COxe2x80x94Rxe2x80x2xe2x80x83xe2x80x83(A)
xe2x80x94CON(CH3)2xe2x80x83xe2x80x83(B)
xe2x80x94CR*R**xe2x80x94Oxe2x80x94Rxe2x80x2xe2x80x3xe2x80x83xe2x80x83(C)
xe2x80x94CR*R**xe2x80x94Oxe2x80x94COxe2x80x94Rxe2x80x2xe2x80x3xe2x80x83xe2x80x83(D)

wherein R* and R** each independently designate hydrogen or C1-3 alkyl, Rxe2x80x2, Rxe2x80x3 and Rxe2x80x2xe2x80x3 each designate C1-6 alkyl or is an aromate Ar1 or Ar2 as defined above.
Preferred compounds of the general formula I are those, wherein Ar1 or Ar2 independently are phenyl or an aromatic 5- or 6-membered heterocyclic ring containing one, two or three heteroatoms selected from oxygen, nitrogen or sulphur, n is 0, 1, 2, or 3, m is 0, 1 or 2, at least one of the groups X is in a position in Ar1 most remote relative to and/or next to the position through which Ar1 is bound to the carbonyl group, and at least one of the groups Y is in a position in Ar2 most remote relative to and/or next to the position through which Ar2 is bound to W.
It is further preferred that A designates O, and Z designates pivaloyl, pivaloyloxymethyl or N,N-dimethylcarbamoyl.
In particular, the bis-aromatic by xcex1,xcex2-unsaturated ketones act by selectively destroying the cells of the microorganisms or cells of multicellular parasites; as will appear from the below discussion and the examples herein, the bis-aromatic xcex1,xcex2-unsaturated ketones in appropriate concentration ranges will selectively kill the microorganisms or the multicellular parasites by destroying the cells of the microorganisms or cells of the multicellular parasites while showing a high degree of tolerance for the host cells which are subjected to exposure to the compounds.
As indicated above, it is contemplated (as described in detail in the following description of mechanism) that the mechanism of action is via interference of the O2-metabolism of the microorganism or parasite in question in that the bis-aromatic xcex1,xcex2-unsaturated ketone inhibits or interferes with the O2-metabolism of the mitochondria (where applicable) of the microorganism such as the parasite or the O2metabolism of the bacteria itself. At the same time, the mitochondria of humans have been found to be able to tolerate the compounds in question in the same concentrations which will inhibit or kill the microorganism or the multicellular parasite. It is this remarkable selectivety of certain classes of bis-aromatic xcex1,xcex2-unsaturated ketones which constitutes the basis of this aspect of the present invention.
Many of the bis-aromatic xcex1,xcex2-unsaturated ketones of the general formula I are novel, and the invention also relates to all such novel bis-aromatic xcex1,xcex2-unsaturated ketones. In the following a some preferred classes of the novel bis-aromatic xcex1,xcex2-unsaturated ketones are defined, and preferred individual compounds among these are discussed specifically.
Because the bis-aromatic xcex1,xcex2-unsaturated ketones used according to the invention have been found to be well tolerated by animal cells, including human cells, such as will be explained in detail in the following, and because these properties are contemplated to be possessed by the broader range of aromatic compounds defined above, the invention opens up the possibility of controlling parasitic diseases not only by administration to the animals, including humans, as therapy or prophylaxis, but also by killing the parasite in its vector by spraying or otherwise applying an aromatic compound of the type defined above, such as a bis-aromatic xcex1,xcex2-unsaturated ketone, in the infected areas so that the vector will take up the compound, whereby the parasite will be subjected to the compound. Thus, one aspect of the invention relates to a method for controlling transmission of parasitic diseases caused by parasites which have part of their life cycles in a vector, comprising applying an aromatic compound as defined above, such as a bis-aromatic xcex1,xcex2-ketone of the general formula I, to a locus which is a habitat of the vector so as to eradicate the parasites. The parasites will, in this case, in particular be Leishmania, Plasmodium, or Trypanosoma, and the eradication of the parasite will, depending on the vector""s tolerance to the compound, take place with or without concomitant eradication of the vector.
When W in the general formula I is xe2x80x94CRxe2x95x90CRxe2x80x94, it may be either cis or trans configured. It is preferred that it is trans configured. It is often preferred that both groups R are hydrogen, but it is contemplated that also bis-aromatic xcex1,xcex2-unsaturated ketones in which one of or both groups R is/are e.g. methyl or ethyl are of great value with respect to the relevant activity and selectivity/tolerability.
With respect to the position of X and/or Y in its/their respective aromate(s), it is highly preferred, and indeed, in number of cases seems to be a condition for a high biological or therapeutic activity against the microorganism in question combined with a high tolerability by animal cells, that at least one of X and Y which is different from hydrogen is positioned in the aromate in a position most remote relative to and/or next to the position through which the aromate is bound to the xcex1,xcex2-unsaturated ketone group. Examples of preferred combinations in this regard are the cases where
Ar1 is phenyl or an aromatic heterocyclic ring containing one, two or three heteroatoms, m is 0, 1 or 2, and X is in a position in Ar1 most remote relative to and/or next to the position through which Ar1 is bound to the carbonyl group;
Ar2 is phenyl or an aromatic heterocyclic ring containing one, two or three heteroatoms, n is 1, 2 or 3, and each Y is in the a position in Ar2 most remote relative to and/or next to the position through which Ar2 is bound to W; or
Ar1 and Ar2 are selected from phenyl and an aromatic heterocyclic ring containing one, two or three heteroatoms, m and n are each 1, 2 or 3, each X is in an position most remote relative to and/or next to the position through which Ar1 is bound to the carbonyl group, and each Y is in a position most remote relative to and/or next to W.
The aromate is suitably phenyl such as illustrated in most of the examples herein, but it is reasonable to contemplate that any of the aromate types mentioned above can be the Ar1 or Ar2 of the bis-aromatic xcex1,xcex2-unsaturated ketone, considering that such aromatic rings will affect the electron density in the unsaturated ketone similarly to the two phenyl rings, and that such aromates will also give possibilities for charge transfer complexes and lipophilic interactions with the target molecule, such as do the two phenyl rings.
Apart from the important substitution with X and/or Y as explained herein, the aromate may carry other substituents which either will not to any substantial extent detract from the useful effect and selectivity of the bis-aromatic xcex1,xcex2-unsaturated ketones, or will enhance these properties or relevant properties related to the use and utility of the bis-aromatic xcex1,xcex2-unsaturated ketones, e.g., their solubility (such as when the bis-aromatic xcex1,xcex2-unsaturated ketones carry a nitrogen-containing basic group or a carboxyl group which can form water-soluble salts with pharmaceutically acceptable counter ions).
Among the bis-aromatic xcex1,xcex2-unsaturated ketones of the general formula I the preferred ones are generally those in which A is O, mainly because of their excellent properties with respect to activity and selectivity/tolerability, such as will appear from the results reported herein. However, it is well known that the oxygen atom in the form of oxy in many biologically active compounds may, with greater or lesser retention of, and indeed in certain cases with enhancement of, the biological activity, be replaced with bioisosteric groups, such as xe2x80x94Sxe2x80x94, xe2x80x94NHxe2x80x94, and xe2x80x94N(C1-6 alkyl)- as mentioned above.
As appears from the discussion herein and the results reported herein, the presence of a particular substituent X or Y or of particular substituents X and Y, preferably in specific positions in the aromate, in particular in the position in the aromate which is remote relative to and/or next to the position of attachment of the aromate, seems to be important to the effect and selectivity of the bis-aromatic xcex1,xcex2-unsaturated ketones. Based upon the above-mentioned general preference for substituents X and Y which contain xe2x80x94Oxe2x80x94 (but taking into consideration that the oxygen atom could be replaced with the a bioisosteric group), this substituent could be called xe2x80x9can oxy-functional substituentxe2x80x9d. While it is presumed that the activity of the oxy-functional substituent is related to the substituent in the xe2x80x9cfreexe2x80x9d form, that is, to hydroxy when A is xe2x80x94Oxe2x80x94, to thiolo when A is xe2x80x94Sxe2x80x94, and to amino or monoalkylamino when A is xe2x80x94NHxe2x80x94 or xe2x80x94N(C1-6-alkyl)-, very interesting results obtained with bis-aromatic xcex1,xcex2-unsaturated ketones of the formula I where X or Y is alkenyloxy raise the intriguing question whether the active form in theses cases is the alkenyloxy-substituted form, or whether the alkenyloxy group is converted to a hydroxy group, maybe even by the microorganism or parasite itself, before the bis-aromatic xcex1,xcex2-unsaturated ketone exerts it action. As will be understood, this possibility is covered by the definition RH above, while the definition of Z, when Z is not hydrogen, is adapted to represent xe2x80x9cprodrugxe2x80x9d forms which, in accordance with well known principles used in the construction of suitable administration embodiments of chemical compounds containing, e.g., free hydro groups as substituents on aromatic rings, will be decomposed in the animal body to result in the corresponding compound in which Z is hydrogen.
In a preferred embodiment, the bis-aromatic xcex1,xcex2-unsaturated ketone has the general formula II
Xmxe2x80x94Phxe2x80x94C(O)xe2x80x94CHxe2x95x90CHxe2x80x94Phxe2x80x94Ynxe2x80x83xe2x80x83II
wherein Ph designates phenyl, and Xm and Yn are as defined above, and each phenyl group may be substituted with one or more substituents selected from halogen; nitro; nitroso; and C1-12, preferably C1-6, straight or branched aliphatic hydrocarbyl which may be saturated or may contain one or more unsaturated bonds selected from double bonds and triple bonds, which hydrocarbyl may be substituted with one or more substituents selected from hydroxy, halogen, amino, and amino which is optionally alkylated with one or two C1-6 alkyl groups.
In these compounds, it is preferred that X and/or Y designates OH or a group ORH, in which RH is as defined above, or OZ*, in which Z* is a masking group which is readily decomposed under conditions prevailing in the animal body to liberate the group OH, in particular one of the groups (A)-(E) as defined above, preferably pivaloyl, pivaloyloxymethyl or N,N-dimethylcarbonyl.
The substituent or substituents on the phenyl group(s) is/are preferably selected from C1-12, preferably C1-6, straight or branched aliphatic hydrocarbyl which may be saturated or may contain one or more unsaturated bonds selected from double bonds and triple bonds, which hydrocarbyl may be substituted with one or more substituents selected from hydroxy, halogen, amino, and amino which is optionally alkylated with one and two C1-6 alkyl groups.
In especially preferred embodiments, the substituent or substituents on the phenyl groups is/are selected from methyl, ethyl, propyl, isopropyl, tert.-butyl, prop-2-enyl, 1,1-dimethylpropyl, 1,1-dimethylprop-2-enyl, 3-methylbutyl, and 3-methylbut-2-enyl.
The host animals to be treated, either to obtain a therapeutic effect, or to obtain a prophylaxis or protection against infection, are primarily vertebrates such as birds, fish and mammals, including humans. It is evident that with respect to some of the microorganisms and multicellular parasites mentioned above, the host to be treated is defined once the microorganism or multicellular parasite is given. Thus, for example, when the microorganism is Leishmania, the hosts to be treated are humans or dogs; when the microorganism is Theileria, the animals to be treated are cattle, sheep and goats; when the microorganism is Eimeria, the animals to be treated are chickens and turkeys.
Based upon findings as explained in the examples below, it is presumed that the mechanism of action of the bis-aromatic xcex1,xcex2-unsaturated ketones of the general formulae I and II above, and prodrugs thereof, is as follows:
The bis-aromatic xcex1,xcex2-unsaturated ketones severely damage the mitochondria of the parasites. Mitochondria are oval-shaped organelles, typically about 2 xcexcm in length and 0.5 xcexcm in diameter, located intracellulary in all organisms except bacteria. Mitochondria have two membrane systems, an outer membrane and an extensive, highly folded inner membrane, hence there are two compartments in mitochondria: the intermembrane space between the inner membrane and the outer membrane, and the matrix, which is bounded by the inner membrane.
Mitochondria are the organelles involved in the O2-metabolism of the cell. Oxidative phosphorylation is the process in which ATP is formed as electrons are transferred from NADH or FADH2 to O2 by a series of electron carriers. This is the major source of ATP in aerobic organisms. Oxidative phosphorylation is carried out by respiratory assemblies located as an integral part of the inner mitochondrial membrane. The outer membrane is quite permeable to most small molecules and ions.
From B. Inoue, K. Inaba, T. Mori, F. Izushi, K. Eto, R Sakai, M. Ogata and K. Utsumi, J. Toxicol. Sci. 7 (1982), 245-254 it is known that echinastin, 4-hydroxychalcone, chalcone, and 3,4xe2x80x2-dihydroxychalcone cause deterioration of respiratory control and oxidative phosphorylation of isolated rat liver mitochondria. The present inventors have found that bis-aromatic xcex1,xcex2-unsaturated ketones and derivatives thereof of the general formula I or II cause deterioration of respiratory control and oxidative phosphorylation of mitochondria of parasites in concentrations that are so small that the mitochondria of the animal cell are not affected.
Due to the interference with the O2-metabolism of the mitochondria the mitochondria are destroyed and as a consequence the cell to which the mitochondria belong is destroyed.
Thus, the compound known as licochalcone A does not appear to exhibit any toxicity in animal cells even at fairly high concentrations, cf. the data given in Example 14 herein. Thus, licochalcone A is an important potential antiparasitic, in particular, antimalarial and antileishmanial drug. However, as appears from the experiments reported in the examples herein, the surprising effect and selectivity found is not limited to licochalcone A, but is characteristic of the class of bis-aromatic xcex1,xcex2-unsaturated ketones discussed herein and, for the reasons given above, is believed to apply more broadly to the aromatic compounds defined above.
Leishmania parasites are transferred through bites from sandflies belonging to the genera Phlebotomus and Lutzomyia. In the gastrointestinal canal of the flies the parasite is transformed from the amastigote phase to the promastigote phase and is propagated. Thereupon the promastigotes migrate to the mouth, especially the salivary glands of the flies and are transferred with the next bite from the fly.
The promastigotes are bound to the macrophage of the infected organism followed by uptake of the parasite into the macrophage where it is transformed to the amastigote phase and multiply inside these cells.
bis-Aromatic xcex1,xcex2-unsaturated ketones as defined herein have been found to have effect on the Leishmania parasite in the amastigote phase as well as in the promastigote phase. This means that the compounds in question are both useful in the prophylaxis of leishmaniasis, because of the effect against the promastigotes, and in the treatment of the disease, because of the effect against the amastigotes. Again, this is believed to apply more broadly to the aromatic compounds defined above.
In cultures, promastigotes multiply with exponential rate the first three days, called the log-phase, and for the following three days the promastigotes are still alive but not multiplying any longer (this phase is called the stationary phase), unless they are transported to another medium. In case the promastigotes are transferred to another medium the log-phase will continue for another three days, and then the promastigotes will enter the stationary phase.
If promastigotes are bound to macrophages in the log-phase, the promastigotes will be killed by the macrophage. On the other hand, if the promastigotes are bound to macrophages in the stationary phase, then the promastigotes are able to infect the cells and multiply inside them.
The stationary phase of the promastigotes, the infective form of the parasite, is generally more sensitive to the bis-aromatic xcex1,xcex2-unsaturated ketones than the log phase of the promastigote, which means that the bis-aromatic xcex1,xcex2-unsaturated ketones are able to prevent infection with the Leishmania parasite; in accordance with the explanation given above, this is believed to apply more broadly to the aromatic compounds defined above.
Bacteria possess a cell wall and a cytoplasmic membrane, but lack mitochondria. Instead, the electron transport and the oxidative phosphorylation, and the latter only in the aerobic bacteria, takes place in the cytoplasmic membrane which then serves the mitochondria-like function in the bacteria.
It is contemplated that the aromatic compounds, such as the bis-aromatic xcex1,xcex2-unsaturated ketones defined herein interfere with the O2-metabolism of the cytoplasmic membrane corresponding to the interference with the O2-metabolism of the mitochondria of higher developed organisms, thereby destroying the bacteria.
As mentioned above, important findings on which the present invention is based are not only the remarkable efficiency of the bis-aromatic xcex1,xcex2-unsaturated ketones with respect to destroying the pathogenic microorganisms, but also the high degree of selectivity which they show with respect to the pathogenic microorganisms as contrasted to animal cells, including human cells. Thus, as will appear from the data given in the examples below, bis-aromatic xcex1,xcex2-unsaturated ketones have been found to be substantially harmless to human cells in concentrations at which they effectively control the parasites. This selectivity was surprising. Moreover, as appears from the examples, a still much higher activity against the microorganisms is found when the microorganisms are present in tissue, such as in cells, such as will be the case in the actual therapeutic use. In many cases, a further increase by a factor 10 in the selectivity is seen.
Preliminary experiments (Example 25) involving oral administration of licochalcone A to mice and rats and injection of licochalcone A to mice indicate that in animals such as mammals, the bis-aromatic xcex1,xcex2-unsaturated ketones which possess a free phenolic hydroxy group will be eliminated from the blood stream already after the first passage to through the liver. This is in accordance with what is known about the metabolism of other phenolic compounds. For this reason, an important aspect of the invention is constituted by compounds in which the phenolic hydroxy group or groups or bioisosteric other group or groups AZ are masked, in other words, the so-called prodrugs, that is, compounds which are readily decomposed under conditions prevailing in the animal body to liberate the free groups which are associated with the active forms of the drugs.
The prodrugs used according to the invention are, e.g., compounds of the general formula I or II in which Z is a group which is readily decomposed under conditions prevailing in the animal body to liberate the group AH. As an important example, when A is O such as is the case in important compounds used according to the invention, it is preferred that Z is a group which is readily decomposed under conditions prevailing in the animal body to liberate the group OH.
The establishment of prodrug forms suitable in connection with particular substituents in drugs is based upon the fact that certain types of groups will tend to be decomposed in the animal body in accordance with various decomposition pathways. Thus, among the above-mentioned specific prodrug groups (A)-(E), the groups (A), (D), and (E) are groups which will be decomposed by esterases to result in the corresponding free group such as the hydroxy group. The group (B) will be subjected to removal of one of the methyl groups in the liver, and the group thus formed will be relatively readily decomposable in plasma. The oxy-containing groups (C) are groups which are relatively labile under acidic conditions and, as thus, are adapted to be decomposed, e.g., under the conditions under which Leishmania amastigotes exist in the human body, that is, in macrophages. Quite generally, the prodrug group Z will be one which prevents the active molecule from being converted, in the liver, to a form which, from a practical point of view, will be inactive and quickly will be eliminated from the animal body, such as the forms where free phenolic OH groups are sulfated in the liver or are coupled to gluconic acid in the liver.
In preferred embodiments, Z is a group selected from the groups (A)-(E) as defined above. Examples of particularly preferred groups Z are pivaloyl, pivaloyloxymethyl and N,N-dimethylcarbamoyl.
The above considerations concerning prodrug derivatives of hydroxy groups in the compounds of the general formula I or II also apply to other hydroxy group-containing aromatic alkylating compounds as defined above.
In the following, valuable and interesting subclasses of the bis-aromatic xcex1,xcex2-unsaturated ketones used according to the invention will be discussed.
Based upon their generally very interesting selective properties, an interesting class of compounds used according to the invention is constituted by compounds of the general formula III 
wherein R2 and R4 designate RH as defined above, or H, one of R*6 and R*8 designate OW* and the other is H, or both R*6 and R*8 designate H, and W* designates H, RH or a group (A)-(E) as defined above, wherein both R* and R** designate H.
Other interesting bis-aromatic xcex1,xcex2-unsaturated ketones used according to the invention have the general formula IV 
wherein R2, R4, R*6, R*8 and OW* are as defined above.
Because of the very interesting properties possessed by licochalcone A, confer the examples which follow, very interesting compounds used according to the invention are bis-aromatic xcex1,xcex2-unsaturated ketones in which the two hydroxy groups in licochalcone A are replaced with a group OW*, in which each W* independently designates H, RH or a group (A)-(E) as defined above, wherein both R* and R** designated H, such as compounds which have the general formula V or VI 
Also, bis-aromatic xcex1,xcex2-unsaturated ketones of the general formula VII 
wherein Z is as defined above, are evidently very interesting compounds. In those compounds, it is preferred that Z designates pivaloyl, pivaloyloxymethyl or N,N-dimethylcarbonyl.
Another interesting class of bis-aromatic xcex1,xcex2-unsaturated ketones has the general formula VIII 
wherein W* is as defined above.
Many of the bis-aromatic xcex1,xcex2-unsaturated ketones of the general formula I are novel compounds, and the invention also relates to all such novel compounds per se.
Among the novel compounds of the invention are the bis-aromatic xcex1,xcex2-unsaturated ketones of the general formula IX 
wherein one of Rxe2x80x26 and Rxe2x80x28 designate A(W*)p and the other designates H, or both designate H, A designates S, N or O, whereby, when A designates S or O, then p designates 1, and when A designates N, then p designates 2, with the proviso that when R2 and R4 both are H, then at least one W* designates a masking group Z as defined above, and with the exception of the known compounds licochalcone A, licochalcone C, 3-[4-hydroxy-5-(1,1-dimethylprop-2-enyl)-2-methoxyphenyl]-1-[4-(methoxymethoxy)phenyl]-2-propen-1-one, 3-[4-acetyloxy-5-(1,1-dimethylprop-2-enyl)-2-methoxyphenyl]-1-[4-(methoxymethoxy)phenyl]-2-propen-1-one, 3-[5-(1,1-dimethylprop-2-enyl)-2,4-dimethoxyphenyl]-1-[4-(methoxy)phenyl]-2-propen-1-one, 3-[4-acetyloxy-5-(1,1-dimethylprop-2-enyl)-2-methoxyphenyl]-1-(4-acetyloxyphenyl)-2-prop-1-one, 3-[2-hydroxy-4-methoxy-3-(3-methylbut-2-enyl)phenyl]-1-[4-[(3,7,11-trimethyl-2,6-dodecatri-10-enyl)oxy]phenyl]-2-prop-1-one, and 2,4-dihydroxy-3-methylchalcone.
Among such novel compounds of the formula IX, very interesting compound are of the general formula X 
wherein R2 and R4 are as defined in claim 41, one of R*8 and R*6 designates OW*, and the other designates H, or both designate H, and W* is as defined above.
Particularly interesting compounds have the general formula XI 
wherein R2, R4 and W* are as defined above. The compounds in which R2 and/or R4 designates methyl, ethyl, propyl, isopropyl, tert.-butyl, prop-2-enyl, 1,1-dimethylpropyl, 1,1-dimethylprop-2-enyl, 3-methylbutyl, or 3-methylbut-2-enyl are especially preferred compounds.
Important novel compounds according to the invention are of the general formula XII 
wherein R2 and W* are as defined above.
Also, the bis-aromatic xcex1,xcex2-unsaturated ketones of the general formula XIII 
wherein RH, R2 and W* are as defined above are interesting novel compounds. Among these, very interesting compounds are those in which R2 designates methyl, ethyl, propyl, isopropyl, tert.-butyl, prop-2-enyl, 1,1-dimethylpropyl, 1,1-dimethylprop-2-enyl, 3-methylbutyl, or 3-methylbut-2-enyl.
Particularly interesting novel bis-aromatic xcex1,xcex2-unsaturated ketones are prodrugs of Licochalcone A of the general formula XIV 
wherein Zxe2x80x2 is one of the groups (A)-(E) as defined above.
Novel bis-aromatic xcex1,xcex2-unsaturated ketones of the general formula XV 
wherein one of Rxe2x80x26 and Rxe2x80x28 designates A(W*)p and the other designates H, or both designate H, W* is as defined above, A designate S, N or O, whereby when A designates S or O then p designates 1, and when A designates N then p designates 2, with the exception of 2,6-methoxychalcone and 2-hydroxy-6-methoxychalcone, form a further interesting class of compounds. Of these compounds, an interesting subclass of bis-aromatic xcex1,xcex2-unsaturated ketones have the general formula XVI 
wherein R2, R4, R*8, R*6 and W* are as defined above.
Among these, interesting novel bis-aromatic xcex1,xcex2-unsaturated ketones have the general formula XVII 
wherein R2, R4 and W* are as defined above, in particular the compounds of the general formula XVIII 
wherein RH, R2, R4 and W* are as defined above. Those compound in which R2 and/or R4 designates methyl, ethyl, propyl, isopropyl, tert.-butyl, prop-2-enyl, 1,1-dimethylpropyl, 1,1-dimethylprop-2-enyl, 3-methylbutyl, or 3-methylbut-2-enyl are especially interesting.
Other novel bis-aromatic xcex1,xcex2-unsaturated ketones have the general formula XIX 
wherein R2 and W* are as defined above. Among these, the compounds in which R2 designates propyl, prop-2-enyl, 1,1-dimethylpropyl, or 1,1-diethylprop-2-enyl are especially interesting.
Another interesting class of novel bis-aromatic xcex1,xcex2-unsaturated ketones have the general formula XX 
wherein A, RH, and R2 is as defined above. Among these, the ones in which R2 designates propyl, prop-2-enyl, 1,1-dimethylpropyl, 1,1-dimethylprop-2-enyl, 3-methylbutyl, or 3-methylbut-2-enyl are especially interesting.
Also, the bisaromatic xcex1,xcex2-unsaturated ketones of the general formula XXI 
wherein A, RH, and W* are as defined above, are interesting novel compounds.
Specific examples of these novel bisaromatic xcex1,xcex2-unsaturated ketones are the ones selected from
2,4-dimethoxy-4xe2x80x2-hydroxy-chalcone,
2,4-diethoxy-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-propoxy-4xe2x80x2-hydroxy-chalcone,
2,4-diisopropoxy-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-butoxy-4xe2x80x2-hydroxy-chalcone,
2,4-di-t-butoxy-4xe2x80x2-hydroxy-chalcone,
2,4-dimethoxy-4xe2x80x2-thiolo-chalcone,
2,4-diethoxy-4xe2x80x2-thiolo-chalcone,
2,4-di-n-propoxy-4xe2x80x2-thiolo-chalcone,
2,4-diisopropoxy-4xe2x80x2-thiolo-chalcone,
2,4-di-n-butoxy-4xe2x80x2-thiolo-chalcone,
2,4-di-t-butoxy-4xe2x80x2-thiolo-chalcone,
2,4-dimethoxy-4xe2x80x2-amino-chalcone,
2,4-diethoxy-4xe2x80x2-amino-chalcone,
2,4-di-n-propoxy-4xe2x80x2-amino-chalcone,
2,4-diisopropoxy-4xe2x80x2-amino-chalcone,
2,4-di-n-butoxy-4xe2x80x2-amino-chalcone,
2,4-di-t-butoxy-4xe2x80x2-amino-chalcone,
2,4-dimethoxy-4xe2x80x2-methylamino-chalcone,
2,4-diethoxy-4xe2x80x2-methylamino-chalcone,
2,4-di-n-propoxy-4xe2x80x2-methylamino-chalcone,
2,4-diisopropoxy-4xe2x80x2-methylamino-chalcone,
2,4-di-n-butoxy-4xe2x80x2-methylamino-chalcone,
2,4-di-t-butoxy-4xe2x80x2-methylamino-chalcone,
2,4-dimethoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,4-diethoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-propoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,4-diisopropoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-butoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-t-butoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,4-dimethoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,4-diethoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,4-di-n-propoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,4-diisopropoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,4-di-n-butoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,4-di-t-butoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,4-dimethoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,4-diethoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,4-di-n-propoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,4-diisopropoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,4-di-n-butoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,4-di-t-butoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,4-dimethoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,4-diethoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,4-di-n-propoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,4-diisopropoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,4-di-n-butoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,4-di-t-butoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,4-dimethoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,4-diethoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,4-dimethoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,4-diethoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,4-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,4-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,4-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,4-dimethoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,4-diethoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,4-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,4-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,4-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,4-dimethoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,4-diethoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,4-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,4-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,4-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,4-diethoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-propoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,4-diisopropoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-butoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,4-di-t-butoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,4-diethoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,4-di-n-propoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,4-diisopropoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,4-di-n-butoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,4-di-t-butoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,4-diethoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,4-di-n-propoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,4-diisopropoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,4-di-n-butoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,4-di-t-butoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,4-diethoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,4-di-n-propoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,4-diisopropoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,4-di-n-butoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,4-di-t-butoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,4-d-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,4-dimethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,4-diethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,4-dimethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,4-diethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,4-dimethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,4-diethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,4-dimethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,4-diethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
and the corresponding ketones in which Z is one of the groups (A)-(E) defined above in particular pivaolyloxymethyl or N,N-dimethylcarbamoyl, such as
2,4-dimethoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diethoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-propoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diisopropoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-butoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-t-butoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,4-dimethoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diethoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-propoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diisopropoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-butoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-t-butoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-dimethoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diethoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diethoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-propoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diisopropoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-butoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-t-butoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-butoxy-5-(1,1-methylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-dimethoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diethoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-propoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diisopropoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-butoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-t-butoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-dimethoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diethoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-propoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diisopropoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-butoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-t-butoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-dimethoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diethoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diethoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-propoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diisopropoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-butoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-t-butoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-dimethoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diethoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-propoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diisopropoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-butoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-t-butoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-dimethoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diethoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-propoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diisopropoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-butoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-t-butoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-dimethoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diethoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diethoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-propoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diisopropoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-butoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-t-butoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylmethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone.
Specific examples of bis-aromatic xcex1,xcex2-unsaturated ketones are:
2-methoxy-4,4xe2x80x2-di-pivaloyloxy-5-methyl-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxy-5-ethyl-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxy-5-propyl-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxy-5-prop-2-enyl-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxy-5-(1,1-dimethylprop-2-enyl)-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxy-5-(1,1-dimethylethyl)-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxymethoxy-5-methyl-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxymethoxy-5-ethyl-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxymethoxy-5-propyl-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxymethoxy-5-propenyl-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)-chalcone,
2-methoxy-4,4xe2x80x2-di-pivaloyloxymethoxy-5-(1,1-dimethylethyl)-chalcone,
2-methoxy-4,4xe2x80x2-di-(N,N-dimethylcarbamoyl)-5-methyl-chalcone,
2-methoxy-4,4xe2x80x2-di-(N,N-dimethylcarbamoyl)-5-ethyl-chalcone,
2-methoxy-4,4xe2x80x2-di-(N,N-dimethylcarbamoyl)-5-propyl-chalcone,
2-methoxy-4,4xe2x80x2-di-(N N-dimethylcarbamoyl)-5-propenyl-chalcone,
2-methoxy-4,4xe2x80x2-di-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)-chalcone,
2-methoxy-4,4xe2x80x2-di-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylethyl)-chalcone,
2-methoxy-4,4xe2x80x2-di-methoxymethoxy-5-methyl-chalcone,
2-methoxy-4,4xe2x80x2-di-methoxymethoxy-5-ethyl-chalcone,
2-methoxy-4,4xe2x80x2-di-methoxymethoxy-5-propyl-chalcone,
2-methoxy-4,4xe2x80x2-di-methoxymethoxy-5-prop-2-enyl-chalcone,
2-methoxy-4,4xe2x80x2-di-methoxymethoxy-5-(1,1-dimethylpropenyl)-chalcone,
2-methoxy-4,4xe2x80x2-di-methoxymethoxy-5-(1,1-dimethylethyl)-chalcone,
2-methoxy-4,4xe2x80x2-di-propenoxy-5-methyl-chalcone,
2-methoxy-4,4xe2x80x2-di-propenoxy-5-ethyl-chalcone,
2-methoxy-4,4xe2x80x2-di-propenoxy-5-propyl-chalcone,
2-methoxy-4,4xe2x80x2-di-propenoxy-5-prop-2-enyl-chalcone,
2-methoxy-4,4xe2x80x2-di-propenoxy-5-(1,1-dimethylpropenyl)-chalcone, and
2-methoxy-4,4xe2x80x2-di-propenoxy-5-(1,1-dimethylethyl)-chalcone.
2,4-dimethoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diethoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-propoxy-4xe2x80x2-(2-prop-2-enyloxy-chalcone,
2,4-diisopropoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-butoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-t-butoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-dimethoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diethoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-propoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diisopropoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-butoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-t-butoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-dimethoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diethoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diethoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-propoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diisopropoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy) chalcone,
2,4-di-n-butoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-t-butoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,4-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone.
2,6-dimethoxy-4xe2x80x2-hydroxy-chalcone,
2,6-diethoxy-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-propoxy-4xe2x80x2-hydroxy-chalcone,
2,6-diisopropoxy-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-butoxy-4xe2x80x2-hydroxy-chalcone,
2,6-di-t-butoxy-4xe2x80x2-hydroxy-chalcone,
2,6-dimethoxy-4xe2x80x2-thiolo-chalcone,
2,6-diethoxy-4xe2x80x2-thiolo-chalcone,
2,6-di-n-propoxy-4xe2x80x2-thiolo-chalcone,
2,6-diisopropoxy-4xe2x80x2-thiolo-chalcone,
2,6-di-n-butoxy-4xe2x80x2-thiolo-chalcone,
2,6-di-t-butoxy-4xe2x80x2-thiolo-chalcone,
2,6-dimethoxy-4xe2x80x2-amino-chalcone,
2,6-diethoxy-4xe2x80x2-amino-chalcone,
2,6-di-n-propoxy-4xe2x80x2-amino-chalcone,
2,6-diisopropoxy-4xe2x80x2-amino-chalcone,
2,6-di-n-butoxy-4xe2x80x2-amino-chalcone,
2,4-di-t-butoxy-4xe2x80x2-amino-chalcone,
2,4-dimethoxy-4xe2x80x2-methylamino-chalcone,
2,6-diethoxy-4xe2x80x2-methylamino-chalcone,
2,6-di-n-propoxy-4xe2x80x2-methylamino-chalcone,
2,6-diisopropoxy-4xe2x80x2-methylamino-chalcone,
2,6-di-n-butoxy-4xe2x80x2-methylamino-chalcone,
2,6-di-t-butoxy-4xe2x80x2-methylamino-chalcone,
2,6-dimethoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,6-diethoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-propoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,6-diisopropoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-butoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-t-butoxy-5-methyl-4xe2x80x2-hydroxy-chalcone,
2,6-dimethoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,6-diethoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,6-di-n-propoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,6-diisopropoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,6-di-n-butoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,6-di-t-butoxy-5-methyl-4xe2x80x2-thiolo-chalcone,
2,6-dimethoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,6-diethoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,6-di-n-propoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,6-diisopropoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,6-di-n-butoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,6-di-t-butoxy-5-methyl-4xe2x80x2-amino-chalcone,
2,6-dimethoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,6-diethoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,6-di-n-propoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,6-diisopropoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,6-di-n-butoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,6-di-t-butoxy-5-methyl-4xe2x80x2-methylamino-chalcone,
2,6-dimethoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,6-diethoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,6-diisopropoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-hydroxy-chalcone,
2,6-dimethoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,6-diethoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,6-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,6-diisopropoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,6-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,6-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-thiolo-chalcone,
2,6-dimethoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,6-diethoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,6-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,6-diisopropoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,6-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,6-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-amino-chalcone,
2,6-dimethoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,6-diethoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,6-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,4-diisopropoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,6-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,6-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-methylamino-chalcone,
2,6-dimethoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,6-diethoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-propoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,6-diisopropoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-butoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,6-di-t-butoxy-5-propyl-4xe2x80x2-hydroxy-chalcone,
2,6-dimethoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,6-diethoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,6-di-n-propoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,6-diisopropoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,6-di-n-butoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,6-di-t-butoxy-5-propyl-4xe2x80x2-thiolo-chalcone,
2,6-dimethoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,6-diethoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,6-di-n-propoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,6-diisopropoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,6-di-n-butoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,6-di-t-butoxy-5-propyl-4xe2x80x2-amino-chalcone,
2,6-dimethoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,6-diethoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,6-di-n-propoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,6-diisopropoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,6-di-n-butoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,6-di-t-butoxy-5-propyl-4xe2x80x2-methylamino-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-propoxy-5-(1,1-methylethyl)-4xe2x80x2-hydroxy-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-hydroxy-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-thiolo-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-amino-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-methylamino-chalcone,
2,6-dimethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,6-diethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-propoxy-5-(1,1dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-hydroxy-chalcone,
2,6-dimethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,6-diethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-thiolo-chalcone,
2,6-dimethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,6-diethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-amino-chalcone,
2,6-dimethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,6-diethoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylprop-2-enyl)-4xe2x80x2-methylamino-chalcone,
and the corresponding ketones in which Z is one of the groups (A)-(E) defined above, in particular pivaolyloxymethyl or N,N-dimethylcarbamoyl, such as
2,6-dimethoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diethoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-propoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diisopropoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-butoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-t-butoxy-4xe2x80x2-pivaloyloxy-chalcone,
2,6-dimethoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diethoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-propoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diisopropoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-butoxy-5-methyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-t-butoxy-5-methyl-4xe2x80x2-pivaloyloxy chalcone,
2,6-dimethoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diethoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diisopropoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-dimethoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diethoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-propoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diisopropoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-butoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-t-butoxy-5-propyl-4xe2x80x2-pivaloyloxy-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivalovloxy-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-di-n-propoxy-5-(1,1-methylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,4-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxy-chalcone,
2,6-dimethoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diethoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-propoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diisopropoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-butoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-di-t-butoxy-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-dimethoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diethoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-propoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diisopropoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-butoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-t-butoxy-5-methyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-dimethoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diethoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diisopropoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,4-dimethoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diethoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-propoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diisopropoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-butoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-t-butoxy-5-propyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-pivaloyloxymethoxy-chalcone,
2,6-dimethoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diethoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-propoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diisopropoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-butoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-t-butoxy-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-dimethoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diethoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-propoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diisopropoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-butoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-t-butoxy-5-methyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-dimethoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diethoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-propoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diisopropoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-dimethoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diethoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-propoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diisopropoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-butoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-t-butoxy-5-propyl-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,4-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(N,N-dimethylcarbamoyl)-chalcone.
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxy-3-methyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxy-3-ethyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxy-3-propyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxy-3-prop-2-enyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxy-3-(1,1-dimethylprop-2-enyl)-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxy-3-(1,1-dimethylethyl)-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxymethoxy-3-methyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxymethoxy-3-ethyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxymethoxy-3-propyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxymethoxy-3-propenyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxymethoxy-3-(1,1-dimethylprop-2-enyl)-chalcone,
2,6-dimethoxy-4xe2x80x2-di-pivaloyloxymethoxy-3-(1,1-dimethylethyl)-chalcone,
2,6-dimethoxy-4xe2x80x2-di-(N,N-dimethylcarbamoyl)-3-methyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-(N,N-dimethylcarbamoyl)-3-ethyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-(N,N-dimethylcarbamoyl)-3-propyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-(N,N-dimethylcarbamoyl)-3-propenyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-(N,N-dimethylcarbamoyl)-3-(1,1-dimethylprop-2-enyl)-chalcone,
2,4-dimethoxy-4xe2x80x2-di-(N,N-dimethylcarbamoyl)-3-(1,1-dimethylethyl)-chalcone,
2,6-dimethoxy-4xe2x80x2-di-methoxymethoxy-3-methyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-methoxymethoxy-3-ethyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-methoxymethoxy-3-propyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-methoxymethoxy-3-prop-2-enyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-methoxymethoxy-3-(1,1-dimethylprop-2-enyl)-chalcone,
2,6-dimethoxy-4xe2x80x2-di-methoxymethoxy-(1,1-dimethylethyl)-chalcone,
2,6-dimethoxy-4xe2x80x2-di-propenoxy-3-methyl-chalcone,
2,4-dimethoxy-4xe2x80x2-di-propenoxy-3-ethyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-propenoxy-3-propyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-propenoxy-3-prop-2-enyl-chalcone,
2,6-dimethoxy-4xe2x80x2-di-propenoxy-3-(1,1-dimethylprop-2-enyl)-chalcone, and
2,6-dimethoxy-4xe2x80x2-di-propenoxy-3-(1,1-dimethylethyl)-chalcone.
Specific examples of bis-aromatic xcex1,xcex2-unsaturated ketones are
2,6-dimethoxy-4xe2x80x2-(2-prop-2-enyloxy-chalcone,
2,6-diethoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-propoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diisopropoxy-4-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-butoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-t-butoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-dimethoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diethoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-propoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diisopropoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-butoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-t-butoxy-5-methyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-dimethoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diethoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-propoxy-5-prop-2-enyl 4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diisopropoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-butoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-t-butoxy-5-prop-2-enyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-dimethoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diethoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-propoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diisopropoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-butoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-t-butoxy-5-propyl-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-dimethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diethoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-propoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-diisopropoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-n-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,6-di-t-butoxy-5-(1,1-dimethylethyl)-4xe2x80x2-(2-prop-2-enyloxy)-chalcone.
2,5-dimethoxy-4xe2x80x2-methoxychalcone,
2,5-diethoxy-4xe2x80x2-methoxychalcone,
2,5-di-n-propoxy-4xe2x80x2-methoxychalcone,
2,5-diisopropoxy-4xe2x80x2-methoxychalcone,
2,5-di-n-butoxy-4xe2x80x2-methoxychalcone,
2,4-di-t-butoxy-4xe2x80x2-methoxychalcone,
2,5-dimethoxy-4xe2x80x2-ethoxychalcone
2,5-diethoxy-4xe2x80x2-ethoxychalcone,
2,5-di-n-propoxy-4xe2x80x2-ethoxychalcone,
2,5-diisopropoxy-4xe2x80x2-ethoxychalcone,
2,5-di-n-butoxy-4xe2x80x2-ethoxychalcone,
2,5-di-t-butoxy-4xe2x80x2-ethoxychalcone,
2,4-dimethoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,5-diethoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,5-di-n-propoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,5-diisopropoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,5-di-n-butoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone,
2,5-di-t-butoxy-4xe2x80x2-(2-prop-2-enyloxy)-chalcone.
2-methoxy-4,4xe2x80x2-dihydroxy-5-methylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-ethylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-propylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-isopropylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-t-butylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-prop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-methylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-ethylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-propylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-isopropylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-t-butylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-prop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-methylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-ethylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-propylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-isopropylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-t-butylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-prop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-but-2-enylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-methylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-ethylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-propylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-isopropylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-t-butylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-prop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-but-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-methylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-ethylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-propylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-isopropylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-t-butylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-prop-2-enylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-but-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-methylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-ethylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-propylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-isopropylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-t-butylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-prop-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-but-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-methylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-ethylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-propylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-isopropylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-t-butylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-prop-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-but-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-methylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-ethylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-propylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-isopropylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-t-butylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-prop-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-but-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-methylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-ethylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-propylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-isopropylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-t-butylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-prop-2-enylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-but-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-methylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-ethylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-propylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-isopropylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-t-butylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-prop-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-but-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-methylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-ethylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-propylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-isopropylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-t-butylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-prop-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-but-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-methylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-ethylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-propylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-isopropylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-t-butylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-prop-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-but-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
and the corresponding ketones in which Z is selected from the groups (A)-(E) as defined above
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-methylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-ethylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-propylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-isopropylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-t-butylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-prop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-methylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-ethylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-propylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-isopropylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-t-butylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-prop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-methylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-ethylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-propylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-isopropylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-t-butylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-prop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-but-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-methylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-ethylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-propylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-isopropylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-t-butylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-prop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-but-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-methylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-ethylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-propylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-isopropylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-t-butylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-prop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-methylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-ethylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-propylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-isopropylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-t-butylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-prop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-methylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-ethylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-propylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-isopropylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-t-butylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-prop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-but-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-methylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-ethylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-propylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-isopropylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-t-butylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-prop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-but-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-methylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-ethylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-propylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-isopropylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-t-butylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-prop-2-enylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-methylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-ethylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-propylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-isopropylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-t-butylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-prop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-methylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-ethylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-propylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-isopropylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-t-butylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-prop-2-enylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-but-2-enylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-methylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-ethylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-propylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-isopropylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-t-butylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-prop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-but-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
Specific examples of bis-aromatic xcex1,xcex2-unsaturated ketones are
2-methoxy-4,4xe2x80x2-dihydroxy-5-methylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-3,5-dimethylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-3,5-dipropylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-3,5-diisopropylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-3,5-di-t-butylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-3,5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dihydroxy-3,5-diprop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-3,5-dibut-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-dimethylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-diethylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-dipropylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-diisopropylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-di-t-butylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-diprop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-dibut-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-dimethylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-diethylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-dipropylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-diisopropylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-di-t-butylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-diprop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-dibut-2-enylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-dimethylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-diethylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-dipropylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-diisopropylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-di-t-butylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-diprop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-dibut-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-3,5-dimethylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-3,5-diethylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-3,5-dipropylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-3,5-diisopropylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-t-butylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-3,5-diprop-2-enylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-3,5-dibut-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-dimethylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-diethylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-dipropylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-diisopropylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-t-butylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-diprop-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-dibut-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-3,5-dimethylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-3,5-diethylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino3,5-dipropylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-3,5-diisopropylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-t-butylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-3,5-diprop-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-3,5-dibut-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-3,5-dimethylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-3,5-diethylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-3,5-dipropylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-3,5-diisopropylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-t-butylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-3,5-diprop-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-3,5-dibut-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dimethylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diethylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino3,5-dipropylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diisopropylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-3,3-di-t-butylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diprop-2-enylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dibut-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dimethylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diethylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dipropylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diisopropylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-di-t-butylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diprop-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dibut-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dimethylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diethylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dipropylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diisopropylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-di-t-butylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diprop-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dibut-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dimethylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diethylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dipropylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diisopropylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-di-t-butylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-diprop-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-3,5-dibut-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
and the corresponding ketones in which Z is selected form the groups (A)-(E) as defined above
2-methoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dimethylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diethylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dipropylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diisopropylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-t-butylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diprop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dibut-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dimethylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diethylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dipropylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diisopropylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-t-butylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diprop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dibut-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dimethylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diethylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dipropylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diisopropylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-t-butylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diprop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dibut-2enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dimethylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diethylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dipropylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diisopropylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-t-butylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-diprop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-dibut-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dimethylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diethylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dipropylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diisopropylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-t-butylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diprop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dibut-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dimethylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diethylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dipropylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diisopropylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-t-butylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diprop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dibut-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dimethylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diethylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dipropylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diisopropylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-t-butylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diprop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dibut-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dimethylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diethylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dipropylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diisopropylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-t-butylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-diprop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-3,5-dibut-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dimethylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diethylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dipropylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diisopropylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-di-t-butylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diprop-2-enylchalcone
2-methoxy-4,4xe2x80x2-(N,N-diethylcarbamoyl)-3,5-dibut-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dimethylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diethylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dipropylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diisopropylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-di-t-butylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diprop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dibut-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2enyl)chalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dimethylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diethylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dipropylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diisopropylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-di-t-butylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diprop-2-enylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dibut-2-enylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dimethylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diethylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dipropylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diisopropylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-di-t-butylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diprop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dibut-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2enyl)chalcone
Specific examples of bis-aromatic xcex1,xcex2-unsaturated ketones are
2-methoxy-6,4xe2x80x2-dihydroxy-5-methylchalcone
2-methoxy-6,4xe2x80x2-dihydroxy-3,5-diethylchalcone
2-methoxy-6,4xe2x80x2-dihydroxy-3,5-dipropylchalcone
2-methoxy-6,4xe2x80x2-dihydroxy-3,5-diisopropylchalcone
2-methoxy-6,4xe2x80x2-dihydroxy-3,5-di-t-butylchalcone
2-methoxy-6,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-6,4xe2x80x2-dihydroxy-3,5-diprop-2-enylchalcone
2-methoxy-6,4xe2x80x2-dihydroxy-3,5-dibut-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-dimethylchalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-diethylchalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-dipropylchalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-diisopropylchalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-di-t-butylchalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-diprop-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-dibut-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-dimethylchalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-diethylchalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-dipropylchalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-diisopropylchalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-di-t-butylchalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-diprop-2-enylchalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-dibut-2-enylchalcone
2-propoxy-6,4xe2x80x2-dihydroxy-3,5-di(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-dimethylchalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-diethylchalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-dipropylchalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-diisopropylchalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-di-t-butylchalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-diprop-2-enylchalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-dibut-2-enylchalcone
2-isopropoxy-6,4xe2x80x2-dihydroxy-3,5-di-(1,1-dimethylprop-2enyl)chalcone
2-methoxy-6-hydroxy-4xe2x80x2-amino-3,5-dimethylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-amino-3,5-diethylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-amino-3,5-dipropylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-amino-3,5-diisopropylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-t-butylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-6-hydroxy-4xe2x80x2-amino-3,5-diprop-2-enylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-amino-3,5-dibut-2-enylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-dimethylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-diethylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-dipropylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-diisopropylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-t-butylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-diprop-2-enylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-dibut-2-enylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-dimethylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-diethylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-dipropylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-diisopropylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-t-butylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-diprop-2-enylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-dibut-2-enylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-3,5-dimethylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-3,5-diethylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-3,5-dipropylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-3,5-diisopropylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-t-butylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-3,5-diprop-2-enylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-3,5-dibut-2-enylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dimethylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diethylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dipropylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diisopropylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diprop-2-enylchalcone
2-methoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dibut-2-enylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dimethylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diethylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dipropylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diisopropylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-di-t-butylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diprop-2-enylchalcone
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dibut-2-enylchalcone.
2-ethoxy-6-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dimethylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diethylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dipropylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diisopropylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-di-t-butylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diprop-2-enylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dibut-2-enylchalcone
2-propoxy-6-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dimethylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diethylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-3,5dipropylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diisopropylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-di-t-butylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-diprop-2-enylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-3,5-dibut-2-enylchalcone
2-isopropoxy-6-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
and the corresponding ketones in which Z is selected from the groups (A)-(E) as defined above
2-methoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dimethylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diethylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dipropylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diisopropylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-t-butylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diprop-2-enylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dibut-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dimethylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diethylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dipropylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diisopropylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-t-butylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diprop-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dibut-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dimethylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diethylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dipropylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diisopropylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-butylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diprop-2-enylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dibut-2-enylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dimethylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diethylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dipropylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diisopropylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-t-butylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-diprop-2-enylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-dibut-2enylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxy-3,5-di-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dimethylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diethylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dipropylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diisopropylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-t-butylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diprop-2-enylchalcone
2-methoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dibut-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dimethylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diethylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dipropylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diisopropylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-t-butylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diprop-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dibut-2-enylchalcone
2-ethoxy-6,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dimethylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diethylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dipropylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diisopropylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-t-butylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3-diprop-2-enylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dibut-2-enylchalcone
2-propoxy-6,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dimethylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diethylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dipropylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diisopropylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-t-butylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-di-(1,1-dimethylpropyl)chalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-diprop-2-enylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-3,5-dibut-2-enylchalcone
2-isopropoxy-6,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dimethylchalcone
2-methoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diethylchalcone
2-methoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dipropylchalcone
2-methoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diisopropylchalcone
2-methoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-di-t-butylchalcone
2-methoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-methoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diprop-2-enylchalcone
2-methoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dibut-2-enylchalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dimethylchalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diethylchalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dipropylchalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diisopropylchalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-di-t-butylchalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diprop-2-enylchalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dibut-2-enylchalcone
2-ethoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dimethylchalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diethylchalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dipropylchalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diisopropylchalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-di-t-butylchalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diprop-2-enylchalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dibut-2-enylchalcone
2-propoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dimethylchalcone
2-isopropoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diethylchalcone
2-isopropoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dipropylchalcone
2-isopropoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diisopropylchalcone
2-isopropoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-di-t-butylchalcone
2-isopropoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-diprop-2-enylchalcone
2-isopropoxy-6,4xe2x80x2-(N,N-dimethylcarbamoyl)-3,5-dibut-2-enylchalcone
2-isopropoxy-6,4xe2x80x2-(N,N dimethylcarbamoyl)-5-(1,1-diethylprop-2-enyl)chalcone
Specific examples of bis-aromatic xcex1,xcex2-unsaturated ketones are
2-methoxy-4,4xe2x80x2-dihydroxy-5-propylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-prop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dihydroxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-propylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-prop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-propylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-prop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-but-2-enylchalcone
2-propoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-propylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-prop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-but-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dihydroxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-propylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-prop-2-enylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-amino-5-but-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-propylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-prop-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-but-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-propylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-prop-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-but-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-propylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-prop-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-but-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-amino-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-propylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-prop-2-enylchalcone
2-methoxy-4-hydroxy-4xe2x80x2-methylamino-5-but-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-propylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-prop-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-but-2-enylchalcone
2-ethoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-propylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-prop-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-but-2-enylchalcone
2-propoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-propylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamido-5-prop-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-but-2-enylchalcone
2-isopropoxy-4-hydroxy-4xe2x80x2-methylamino-5-(1,1-dimethylprop-2-enyl)chalcone
and the corresponding ketons in which Z is selected from the groups (A)-(E) as defined above
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-propylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-prop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-propylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-prop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-propylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-prop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-but-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-propylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-prop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-but-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-propylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-prop-2-enylchalcone
2-methoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-propylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-prop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-propylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-prop-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-but-2-enylchalcone
2-propoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-propylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-prop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-but-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-dipivaloyloxymethoxy-5-(1,1-dimethylprop-2-enyl)chalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-propylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-prop-2-enylchalcone
2-methoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-propylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-prop-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-but-2-enylchalcone
2-ethoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-propylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-prop-2-enylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-but-2-enylchalcone
2-propoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-propylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylpropyl)chalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-prop-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-but-2-enylchalcone
2-isopropoxy-4,4xe2x80x2-(N,N-dimethylcarbamoyl)-5-(1,1-dimethylprop-2-enyl)chalcone
The administration route of the aromatic compound as defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketones of the general formula I, may be of any suitable route which leads to a concentration in the blood corresponding to a therapeutic concentration. Thus, e.g., the following administration routes may be applicable although the invention is not limited thereto: the oral route, the parenteral route, the cutaneous route, the nasal route, the rectal route, the vaginal route and the ocular route. It should be clear to a person skilled in the art that the administration route is dependent on the compound in question, particularly, the choice of administration route depends on the physico-chemical properties of the compound together with the age and weight of the patient and on the particular disease and the severity of the same.
The aromatic compounds as defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketones or derivatives thereof, may be contained in any appropriate amount in a pharmaceutical composition, and are generally contained in an amount of about 1-95% by weight of the total weight of the composition. The composition may be presented in a dosage form which is suitable for the oral, parenteral, rectal, cutaneous, nasal, vaginal and/or ocular administration route. Thus, the composition may be in form of, e.g., tablets, capsules, pills, powders, granulates, suspensions, emulsions, solutions, gels including hydrogels, pastes, ointments, creams, plasters, drenches, delivery devices, suppositories, enemas, injectables, implants, sprays, aerosols and in other suitable form.
The pharmaceutical compositions may be formulated according to conventional pharmaceutical practice, see, e.g., xe2x80x9cRemington""s Pharmaceutical Sciencesxe2x80x9d and xe2x80x9cEncyclopedia of Pharmaceutical Technologyxe2x80x9d, edited by Swarbrick, J. and J. C. Boylan, Marcel Dekker, Inc., New York, 1988.
Pharmaceutical compositions according to the present invention may be formulated to release the active compound substantially immediately upon administration or at any substantially predetermined time or time period after administration. The latter type of compositions are generally known as controlled release formulations.
In the present context, the term xe2x80x9ccontrolled release formulationxe2x80x9d embraces
i) formulations which create a substantially constant concentration of the drug within the body over an extended period of time,
ii) formulations which after a predetermined lag time create a substantially constant concentration of the drug within the body over an extended period of time,
iii) formulations which sustain drug action during a predetermined time period by maintaining a relatively, constant, effective drug level in the body with concomitant minimization of undesirable side effects associated with fluctuations in the plasma level of the active drug substance (sawtooth kinetic pattern),
iv) formulations which attempt to localize drug action by, e.g., spatial placement of a controlled release composition adjacent to or in the diseased tissue or organ,
v) formulations which attempt to target drug action by using carriers or chemical derivatives to deliver the drug to a particular target cell type.
Controlled release formulations may also be denoted xe2x80x9csustained releasexe2x80x9d, xe2x80x9cprolonged releasexe2x80x9d, xe2x80x9cprogrammed releasexe2x80x9d, xe2x80x9ctime releasexe2x80x9d, xe2x80x9crate-controlledxe2x80x9d and/or xe2x80x9ctargeted releasexe2x80x9d formulations.
Controlled release pharmaceutical compositions may be presented in any suitable dosage forms, especially in dosage forms intended for oral, parenteral, cutaneous nasal, rectal, vaginal and/or ocular administration.
Administration of the aromatic compounds defined above, such as bis-aromatic xcex1,xcex2-unsaturated ketones in form of a controlled release formulation is especially preferred in such cases where the compound in question
i) has a narrow therapeutic index [i.e. the difference between the plasma concentration leading to harmful side effects or toxic reactions and the plasma concentration leading to a therapeutic effect is small; in general, the therapeutic index, TI, is defined as the ratio of median lethal dose (LD50) to median effective dose (ED50)],
ii) has a narrow absorption window in the gastrointestinal tract. In such cases, it is important that the intact do se of the aromatic compound reaches the site of absorption in order to avoid a substantially uniform distribution of the compound administered in the whole gastrointestinal tract,
iii) has a very short biological half-live so that frequent dosing during a day is required in order to sustain the plasma level at a therapeutic level, or
iv) in cases where it is desirable to enable preparation of a pharmaceutical composition intended for use only once or twice daily or even less frequent with the purpose of reducing patient compliance problems,
v) in cases where it is desirable to avoid peak concentrations in the plasma so that harmful side or toxic effects related to such high concentrations can be substantially reduced,
vi) in cases where it is desirable to avoid fluctuations in plasma concentration of the compound administered (in order to even out any peak and valley concentration).
In general, two basically different strategies can be applied in order to obtain a controlled release formulation in which the rate of release outweighs the rate of metabolism of the compound in question.
In the first strategy, the principle aims at changing the properties of the active drug substance by converting the substance into a masked form. The compounds of the above formulae in which Z is one of the groups (A)-(E) are representatives of this strategy.
In the second strategy, controlled release is obtained by appropriate selection of various formulation parameters and ingredients, including, e.g. various types of controlled release compositions and coatings (formulation-method).
As mentioned above, the first strategy comprises use of the prodrug principle, i.e. converting the active drug substance into a per se inactive derivative which, upon administration to the organism, within the body of the organism by an enzymatic or non enzymatic process releases the active drug substance so that the drug substance can exert its therapeutic effect. By proper choice of the prodrug it is possible to obtain a prodrug which releases the active drug substance with a controlled rate so that it thereby is possible to extend the effect of the drug in the body.
The other strategy comprises the use of the active drug substance per se and then formulate the active drug substance together with appropriate excipients into a pharmaceutical composition which upon administration of the composition to the organism releases the active substance in a controlled manner. Examples include single or multiple unit tablet or capsule compositions, oil solutions, suspensions, emulsions, microcapsules, microspheres, nanoparticles, liposomes, delivery devices such as those intended for oral, parenteral, cutaneous, nasal, vaginal or ocular use.
It will be appreciated that a combination of the above-mentioned two methods can be used in controlled release compositions, comprising the aromatic compounds defined above, such as bis-aromatic xcex1,xcex2-unsaturated ketones, according to the invention, e.g., by using a prodrug of the compound in question and then formulating according to the principles mentioned above.
In the present context every pharmaceutical composition is an actual drug delivery system, since upon administration it presents the active drug substance to the body of the organism.
Solid Dosage Forms for Oral Use
Formulations for oral use include tablets which contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients. These excipients may be, for example,
inert diluents or fillers, such as sucrose, sorbitol, sugar, mannitol, microcrystalline cellulose, starches including potato starch, calcium carbonate, sodium chloride, lactose, calcium phosphate, calcium sulfate or sodium phosphate;
granulating and disintegrating agents, for example, cellulose derivatives including microcrystalline cellulose, starches including potato starch, croscarmellose sodium, alginates or alginic acid;
binding agents, for example, sucrose, glucose, sorbitol, acacia, alginic acid, sodium alginates, gelatin, starch, pregelatinized starch, microcrystalline cellulose, magnesium aluminum silicate, carboxymethylcellulose sodium, methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, polyvinylpyrrolidone or polyethylene glycol; and
lubricating agents, including glidants and antiadhesives, for example, magnesium stearate, zinc stearate, stearic acid, silicas, hydrogenated vegetable oils or talc.
Other pharmaceutically acceptable excipients can be colorants, flavouring agents, plasticizers, humectants, buffering agents etc.
The tablets may be uncoated or they may be coated by known techniques, optionally to delay disintegration and absorption in the gastrointestinal tract and thereby providing a sustained action over a longer period. The coating may be adapted to release the active drug substance in a predetermined pattern, e.g. in order to achieve a controlled release formulation (see below) or it may be adapted not to release the active drug substance until after passage of the stomach (enteric coating). The coating may be a sugar coating, a film coating (e.g. based on hydroxypropyl methylcellulose, methylcellulose, methyl hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, acrylate copolymers (Eudragit E(copyright)), polyethylene glycols and/or polyvinylpyrrolidone) or an enteric coating (e.g. based on methacrylic acid copolymer (Eudragit(copyright) L and S), cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, shellac and/or ethylcellulose).
Furthermore, a time delay material such as, e.g., glyceryl monostearate or glyceryl distearate may be employed.
In addition, the solid tablet compositions as mentioned above may be provided with a coating adapted to protect the composition from unwanted chemical changes, e.g. chemical degradation, prior to the release of the active drug substance.
The coating may be applied on the solid dosage form in a similar manner as that described in xe2x80x9cAqueous film coatingxe2x80x9d by James A. Seitz in xe2x80x9cEncyclopedia of Pharmaceutical Technologyxe2x80x9d, Vol 1, pp. 337-349 edited by Swarbrick, J. and J. C. Boylan, Marcel Dekker, Inc., New York, 1988.
Formulations for oral use may also be presented as chewing tablets, or as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, potato starch, lactose, microcrystalline cellulose, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example, peanut oil, liquid paraffin, or olive oil.
Powders and granulates may be prepared using the ingredients mentioned above under tablets and capsules in a conventional manner using, e.g., a mixer, a fluid bed apparatus or a spray drying equipment.
Controlled Release Oral Dosage Forms
Controlled release compositions for oral use may, e.g., be constructed to release the active drug substance by controlling the dissolution and/or the diffusion of the active drug substance.
Dissolution or diffusion controlled release can be achieved by appropriate coating of a tablet, capsule, pellet or granulate formulation of the aromatic compounds defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketones, or by incorporating the compound in question in, e.g., an appropriate matrix.
A controlled release coating may comprise one or more of the coating substances mentioned above and/or, e.g., shellac, beeswax, glycowax, castor wax, carnauba wax, stearyl alcohol, glyceryl monostearate, glyceryl distearate, glycerol palmitostearate, ethylcellulose, acrylic resins, dl-polylactic acid, cellulose acetate butyrate, polyvinyl chloride, polyvinyl acetate, vinyl pyrrolidone, polyethylene, polymethacrylate, methylmethacrylate, 2-hydroxymethacrylate, methacrylate hydrogels, 1,3-butylene glycol, ethylene glycol methacrylate and/or polyethylene glycols.
In a controlled release matrix formulation of the aromatic compounds defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketones, the matrix material may comprise, e.g., hydrated metylcellulose, carnauba wax and stearyl alcohol, carbopol 934, silicone, glyceryl tristearate, methyl acrylate-methyl methacrylate, polyvinyl chloride, polyethylene and/or halogenated fluorocarbon.
A controlled release composition of the aromatic compound defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketones, may also be in the form of a buoyant tablet or capsule, i.e. a tablet or capsule which upon oral administration floats on top of the gastric content for a certain period of time. A buoyant tablet formulation of the compound in question can be prepared by granulating a mixture of the drug, excipients and 20-75% w/w of hydrocolloids, such as hydroxyethylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose. The obtained granules can then be compressed into tablets. On contact with the gastric juice, the tablet can form a substantially water-impermeable gel barrier around its surface. This gel barrier takes part in maintaining a density of less than one, thereby allowing the tablet to remain buoyant in the gastric juice.
Fluid/liquid Compositions
Powders, dispersible powders or granules suitable for preparation of an aqueous suspension by addition of water are also convenient dosage forms. Formulation as a suspension provides the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives.
Suitable dispersing or wetting agents are, for example, naturally-occurring phosphatides, as e.g. lecithin, or condensation products of ethylene oxide with e.g. a fatty acid, a long chain aliphatic alcohol or a partial ester derived from fatty acids and a hexitol or a hexitol anhydrides, for example, polyoxyethylene stearate, polyoxyethylene sorbitol monooleate, polyoxyethylene sorbitan monooleate etc.
Suitable suspending agents are, for example, sodium carboxymethylcellulose, methylcellulose, sodium alginate etc.
Parenteral Compositions
The pharmaceutical composition may also be administered parenterally by injection, infusion or implantation (intravenous, intramuscular, intraarticular, subcutaneous or the like) in dosage forms, formulations or e.g. suitable delivery devices or implants containing conventional, non-toxic pharmaceutically acceptable carriers and adjuvants.
The formulation and preparation of such compositions is well-known to those skilled in the art of pharmaceutical formulation. Specific formulations can be found in the textbook entitled xe2x80x9cRemington""s Pharmaceutical Sciencesxe2x80x9d.
Compositions for parenteral use may be presented in unit dosage forms, e.g. in ampoules, or in vials containing several doses and in which a suitable preservative may be added (see below). The composition may be in form of a solution, a suspension, an emulsion, an infusion device or a delivery device for implantation or it may be presented as a dry powder to be reconstituted with water or another suitable vehicle before use. Apart from the active drug substance, the compositions may comprise suitable parenterally acceptable carriers and/or excipients or the active drug substance may be incorporated into microspheres, microcapsules, nanoparticles, liposomes or the like for controlled release. Furthermore, the composition may, in addition, conveniently comprise suspending, solubilizing, stabilizing, pH-adjusting agents and/or dispersing agents.
As indicated above, the pharmaceutical compositions according to the invention may comprise the active drug substances in the form of a sterile injection. To prepare such a composition, the suitable active drug substances are dissolved or suspended in a parenterally acceptable liquid vehicle. Among acceptable vehicles and solvents that may be employed are water, water adjusted to a suitable pH by addition of an appropriate amount of hydrochloric acid, sodium hydroxide or a suitable buffer, 1,3-butanediol, Ringer""s solution and isotonic sodium chloride solution. The aqueous formulation may also contain one or more preservatives, for example, methyl, ethyl or n-propyl p-hydroxybenzoate. In cases where the aromatic compound defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketone, is only sparingly or slightly soluble in water, a dissolution enhancing or solubilizing agent can be added or the solvent may apart from water comprise 10-60% w/w of propylene glycol or the like.
Controlled Release Parenteral Compositions
As mentioned above under the heading parenteral compositions, controlled release parenteral compositions may be in form of aqueous suspensions, microspheres, microcapsules, magnetic microspheres, oil solutions, oil suspensions, emulsions or the active drug substance may be incorporated in biocompatible carrier(s), liposomes, nanoparticles, implants or infusion devices.
Materials for use in the preparation of microspheres and/or microcapsules are, e.g., biodegradable/bioerodible polymers such as polyglactin, poly-(isobutyl cyanoacrylate), poly(2-hydroxyethyl-L-glutamine) and poly(lactic add).
Biocompatible carriers which may be used when formulating a controlled release parenteral formulation are, e.g., carbohydrates such as dextrans, proteins such as albumin, lipoproteins or antibodies.
Materials for use in implants are, e.g., non-biodegradable as, e.g., polydimethylsiloxane, or biodegradable such as,e.g., poly(caprolactone), poly(actic acid), poly(glycolic acid) or poly(ortho esters).
Rectal Compositions
For rectal application, suitable dosage forms for a composition include suppositories (emulsion or suspension type), and rectal gelatin capsules (solutions or suspensions). In a typical suppository formulation, the active drug compounds are combined with an appropriate pharmaceutically acceptable suppository base such as cocoa butter, esterified fatty acids, glycerinated gelatin, and various water-soluble or dispersible bases like polyethylene glycols and polyoxyethylene sorbitan fatty acid esters. Various additives like, e.g., enhancers or surfactants may be incorporated.
Nasal Compositions
For nasal application, typical dosage forms include nasal sprays and aerosols for inhalation. In a typically nasal formulation, the active ingredients are dissolved or dispersed in a suitable vehicle. The pharmaceutically acceptable vehicles and excipients and optionally other pharmaceutically acceptable materials present in the composition such as diluents, enhancers, flavouring agents, preservatives etc. are all selected in accordance with conventional pharmaceutical practice in a manner understood by the persons skilled in the art of formulating pharmaceuticals.
Percutaneous and Topical Compositions
The pharmaceutical compositions may also be administered topically on the skin for percutaneous absorption in dosage forms or formulations containing conventionally non-toxic pharmaceutical acceptable carriers and excipients including microspheres and liposomes. The formulations include creams, ointments, lotions, liniments, gels, hydrogels, solutions, suspensions, sticks, sprays, pastes, plasters and other kinds of transdermal drug delivery systems. The pharmaceutically acceptable carriers or excipients may include emulsifying agents, antioxidants, buffering agents, preservatives, humectants, penetration enhancers, chelating agents, gelforming agents, ointment bases, perfumes and skin protective agents.
Examples of emulsifying agents are naturally occurring gums, e.g. gum acacia or gum tragacanth, naturally occurring phosphatides, e.g. soybean lecithin and sorbitan monooleate derivatives.
Examples of antioxidants are butylated hydroxy anisole (BHA), ascorbic acid and derivatives thereof, tocopherol and derivatives thereof, butylated hydroxy anisole and cysteine.
Examples of preservatives are parabens, such as methyl or propyl p-hydroxybenzoate and benzalkonium chloride.
Examples of humectants are glycerin, propylene glycol, sorbitol and urea.
Examples of penetration enhancers are propylene glycol, DMSO, triethanolamine, N,N-dimethylacetamide, N,N-dimethylformamide, 2-pyrrolidone and derivatives thereof, tetrahydrofurfuryl alcohol and Azone(copyright).
Examples of chelating agents are sodium EDTA, citric acid and phosphoric acid.
Examples of gel forming agents are Carbopol, cellulose derivatives, bentonite, alginates, gelatin and polyvinylpyrrolidone.
Examples of ointment bases are beeswax, paraffin, cetyl palmitate, vegetable oils, sorbitan esters of fatty acids (Span), polyethylene glycols, and condensation products between sorbitan esters of fatty acids and ethylene oxide, e.g. polyoxyethylene sorbitan monooleate (Tween).
The pharmaceutical compositions mentioned above for topical administration on the skin may also be used in connection with topical administration onto or dose to the infected parts of the body which is to be treated. The compositions may be any suitable medicated mass adapted for direct application or for introduction into relevant orifice(s) of the body, e.g. the rectal, urethral, vaginal or oral orifices. The compositions may simply be applied directly onto the infected part, e.g. the mucosa. In certain cases it might be applied by means of special drug delivery devices such as dressings or alternatively plasters, pads, sponges, strips or other forms of suitable flexible material.
Controlled Release Percutaneous and Topical Compositions
In general, four different approaches are applicable in order to provide rate control over the release and transdermal permeation of a drug compound. These approaches are: membrane-moderated systems, adhesive diffusion-controlled systems, matrix dispersion-type systems and microreservoir systems. It is appreciated that a controlled release percutaneous and/or topical composition may be obtained by using a suitable mixture of the above-mentioned approaches.
In a membrane-moderated system, the active drug substance is present in a reservoir which is totally encapsulated in a shallow compartment molded from a drug-impermeable laminate, such as a metallic plastic laminate, and a rate-controlling polymeric membrane such as a microporous or a non-porous polymeric membrane, e.g., ethylene-vinyl acetate copolymer. The active drug substance is only permitted to be released through the rate-controlling polymeric membrane. In the drug reservoir, the active drug substance may either be dispersed in a solid polymer matrix or suspended in an unleachable, viscous liquid medium such as silicone fluid. On the external surface of the polymeric membrane, a thin layer of an adhesive polymer is applied to achieve an intimate contact of the transdermal system with the skin surface. The adhesive polymer is preferably a polymer which is hypo allergenic and compatible with the active drug substance.
In an adhesive diffusion-controlled system, a reservoir of the active drug substance is formed by directly dispersing the active drug substance in an adhesive polymer and thenxe2x80x94by, e.g., solvent castingxe2x80x94spreading the adhesive containing the active drug substance onto a flat sheet of substantially drug-impermeable metallic plastic backing to form a thin drug reservoir layer.
A matrix dispersion-type system is characterized in that a reservoir of the active drug substance is formed by substantially homogeneously dispersing the active drug substance in a hydrophilic or lipophilic polymer matrix and then, the drug-containing polymer is molded into disc with a substantially wellefined surface area and controlled thickness. The adhesive polymer is spread along the circumference to form a strip of adhesive around the disc.
A microreservoir system may be considered as a combination of the reservoir and matrix dispersion type systems. In this case, the reservoir of the active substance is formed by first suspending the drug solids in an aqueous solution of water-soluble polymer and then dispersing the drug suspension in a lipophilic polymer to form a multiplicity of unleachable, microscopic spheres of drug reservoirs.
Compositions for Administration to the Eye
Formulations for administration to the eye may be presented in the form of eye drops, lotions, ointments or delivery. devices. Typically, the composition comprises the active drug substance in combination with pharmaceutically inert vehicles or the active drug substance is incorporated in a suitable carrier system. Pharmaceutically inert vehicles and/or excipients for the preparation of eye drops include, e.g., buffering agents such as boric acid or borates, pH adjusting agents to obtain optimal stability or solubility of the active drug substance, tonicity adjusting agents such as sodium chloride or borates, viscosity adjusting agents such as hydroxypropyl cellulose, methylcellulose, polyvinylpyrrolidone, polyvinyl alcohols or polyacrylamide, oily vehicle such as vehicles comprising arachis oil, castor oil and/or mineral oil. Emulsions and suspensions of the active drug substance may also be presented in form of eye drops. In these cases, the composition may furthermore comprise stabilizing, dispersing, wetting, emulsifying and/or suspending agents. Eye lotions and eye ointments may comprise pharmaceutically acceptable carriers and/or excipients such as those used in an eye drop composition or in other relevant topical composition such as, e.g., ointments, creams and lotions.
In general, an aqueous eye drop composition may be prepared by dissolving the active drug substance (or preferably a water-soluble salt or prodrug thereof) in sterile water in a specific concentration, optionally adjusting pH to a suitable pH by adding an appropriate amount of an appropriate buffer solution or hydrochloric add or sodium hydroxide, optionally adding a preservative such as phenethanol, optionally adding a viscosity increasing agent such as methylcellulose, and subject the resulting solution to filtration followed by sterilization e.g. by autoclaving or by membrane filtration.
The formulation and preparation of the above-mentioned compositions are well-known to those skilled in the art of pharmaceutical formulation Specific formulations can be found in xe2x80x9cRemington""s Pharmaceutical Sciencesxe2x80x9d.
Addition to Animal Feed and Fish Water
As mentioned above, the aromatic compounds defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketones or derivatives thereof, may be most valuable for controlling parasites in e.g. cattle, birds and fish. This may be carried out, e.g. by adding the compound in question to the feed or the drinking water of the animals, or when the animals to be treated are fish, the compound in question may also be added to the fish water.
Dosages
The dosage of an appropriate compound as defined herein or derivative thereof depends on the administration method, the disease to be treated and the severity of same, and whether the disease is to be treated or prevented, as well as the age and weight of the person or animal to be treated.
The bis-aromatic xcex1,xcex2-ketones are preferably administered in an amount of about 0.1-30 mg per kg body weight per day, such as about 0.5-15 mg per kg body weight per day. As mentioned above, the compound in question may be administered orally in the form of tablets, capsules, elixis or syrups, or rectally in the form of suppositories. Parenteral administration of the aromatic compound defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketone, is suitably performed in the form of saline solutions of the ketones (or salts thereof) or with the compound incorporated into liposomes. In cases where the compound in itself is not sufficiently soluble to be dissolved, an acid addition salt of a basic compound of the formula I (that is, a compound of the formula I in which either an aromatic ring or a substituent contains a basic nitrogen atom) can be used, or a solubilizer such as ethanol can be applied.
Acid addition salts of basic compounds of the formula II, such as compounds containing basic substituents, e.g. dimethylamino, on the aromatic ring, or compounds containing an aromatic ring with basic properties, such as pyridine, are also interesting compounds and may be of special value in cases where a water-soluble compound is preferred, e.g. as sprays in transmission control, or in solutions for injection. The acid addition salts, may, e.g. be hydrochlorides, oxalates, malonates, fumarates, citrates, acetates, propionates, formates, sulphates. The acid addition salts may be easily prepared from the corresponding basic compounds by addition of the appropriate acid.
Oral Administration
For compositions adapted for oral administration for systemic use, the dosage is normally 1 mg to 1 g per dose administered 1-4 times daily for 1 week to 12 months depending on the disease to be treated.
The dosage for oral administration for the treatment of parasitic diseases is normally 1 mg to 1 g per dose administered 1-2 times daily for 1-4 weeks, in particular the treatment of malaria is to be continued for 1-2 weeks whereas the treatment of leishmaniasis will normally be carried out for 3-4 weeks.
The dosage for oral administration for the treatment of bacterial diseases is normally 1 mg to 1 g per dose administered 1-4 times daily for 1 week to 12 months; in particular, the treatment of tuberculosis will normally be carried out for 6-12 months.
The dosage for oral administration of the composition in order to prevent diseases, in particular, parasitic diseases, is normally 1 mg to 75 mg per kg body weight per day. The dosage may be administered once or twice daily for a period starting 1 week before the exposure to the disease until 4 weeks after the exposure.
Rectal Administration
For compositions adapted for rectal use for preventing diseases, a somewhat higher amount of aromatic compounds, such as bis-aromatic xcex1,xcex2-unsaturated ketones or derivatives thereof is usually preferred, i.e. from approximately 1 mg to 100 mg per kg body weight per day.
Parenteral Administration
For parenteral administration a dose of about 0.1 mg to about 50 mg per kg body weight per day is convenient.
For intravenous administration a dose of about 0.1 mg to about 20 mg per kg body weight per day administered for 1 day to 3 months is convenient.
For intraarticular administration a dose of about 0.1 mg to about 20 mg per kg body weight per day is usually preferable.
For parenteral administration in general, a solution in an aqueous medium of 0.5-2% or more of the active ingredients may be employed.
Percutaneous Administration
For topical administration on the skin a dose of about 1 mg to about 5 g administered 1-10 times daily for 1 week to 12 months is usually preferable.
Transmission Control
As mentioned above, the use of the aromatic compounds defined above, such as the bis-aromatic xcex1,xcex2-unsaturated ketones, or derivatives thereof in controlling parasites in their vectors is an interesting and promising aspect of the present invention. The principle is to destroy the parasites in their vectors, thereby preventing transmission of the disease.
The data presented herein demonstrate clearly that the promastigote stage, the same form of the parasite which is present in the sandfly vector, of the L. major and L. donovani parasite, is killed by the bis-aromatic xcex1,xcex2-unsaturated ketones or derivatives thereof.
For example, spraying endemic areas for malaria or leishmania or other protozoal diseases transmitted by their respective vectors will be of an attractive means of controlling such important parasitic diseases.
For the compounds mentioned above containing a double bond, the corresponding compounds in which the bond is a triple bond such as discussed in connection with the general formula I are also very interesting and should be considered correspondingly disclosed herein in connection with each and every structural formula shown herein and each and every compound named herein.
It many cases, it will be preferred to administer the compound defined herein together with another antiparasitic, antimycotic or antibiotic drug, thereby reducing the risk of development of resistance against the conventional drugs, and reducing the amount of each of the drugs to be administered, thus reducing the risk of side effects caused by the conventional drugs. Important aspects of this is the use of the compound against Leishmania, where the compound I is combined with another antileishmanial drug, or the antimalarial use of the compound I where the compound I is used together with another antimalarial drug.
As examples of other antileishmanial drugs to be combined with the compounds defined herein may be mentioned pentavalent antimony-sodium gluconate and allopurinol.
As examples of other antimalarial drugs to be combined with the compounds defined herein may be mentioned chloroquine and derivatives thereof, quinine, proguanil, cycloguanil, mefloquine, pyrimethamine and artemisinin.
As an example of an additional antibiotic drug to be combined with the compounds defined herein may be mentioned an antituberculous drug such as isoniazide, ethambutol, pyrazinamide, and rifampicin.
As examples of additional antimycotic drugs to be combined with the compounds defined herein may be mentioned amphotericin B, muconarcidol, griseofulvin, and miconazol.
As examples of additional antibabesial drugs to be combined with the compounds defined herein may be mentioned quinuronium sulfate, pentamidine isethionate, imidocarb or diminazene.
As examples of additional anticoccidial drugs to be combined with the compounds defined herein may be mentioned fulfonamides, amprocid and coccidiostatic agents such as inomycins, in particular monensin and salinomycin.
As examples of additional drugs against fish parasites to be combined with the compounds defined herein may be mentioned benzimidazol and formaldehyde.
One general advantage of the compounds defined herein are their broad-spectered character, which makes it possible to use the compounds as sole medication in cases where the host to be treated is infected with, or suspected to be infected with, more than one of the bacteria and parasites discussed herein, or to use them as supplements to known antibacterial agents and antiparasitic agents in order to reduce the dose of the conventional antibiotics or antiparasitic agents, thus reducing the risk of side effects, in addition to the above-mentioned advantages with respect to reduction of drug resistance development.
In particular for prophylaxis, the broad-spectered character of the compounds of the general formula I is of great advantage, and may be further augmented by combination with more than one antibacterial or antiparasitic agent, such as combination with both another antileishmanial agent and another antimalarial agent. It is justified to presume that also the other aromatic compounds defined herein will show the same valuable broad-spectered character.
While the above-mentioned compounds of the general formula I are predominantly compounds in which W is xe2x80x94CRxe2x95x90CRxe2x80x94, it should be borne in mind that compounds which correspond to each of the compounds mentioned above, but in which W is xe2x80x94Cxe2x89xa1Cxe2x80x94, are also important compounds according to the invention.
As mentioned above, a number of the compounds of the general formula I are known, whereas many of the compounds of the general formula I are novel compounds. The known compounds may be isolated or synthesized in accordance with methods known from the literature or methods analogous thereto. The novel compounds may, likewise, be produced by methods known per se or methods which are analogous to such methods. A number of preferred and interesting methods for preparing the compounds of the general formula I are discussed in the following:
In a process a), compounds of the formula I in which W is xe2x80x94CHxe2x95x90CHxe2x80x94 are prepared by reacting a ketone of the general formula Ixe2x80x2
Xxe2x80x94Ar1xe2x80x94COxe2x80x94CH3xe2x80x83xe2x80x83Ixe2x80x2
with an aldehyde of the general formula Ixe2x80x3
HCOxe2x80x94Ar2xe2x80x94Yxe2x80x83xe2x80x83Ixe2x80x3
This reaction, which is a condensation reaction, is suitably carried out under acid or base catalyzed conditions. A review of such processes may be found in Nielsen, A. T., Houlihahn, W. J., Org. React. 16, 1968, p 1-444. In particular the method described by Wattanasin, S. and Murphy, S., Synthesis (1980) 647 has been found to be very successful.
The reaction may suitably be carried out in protic organic solvents, such as lower alcohols (e.g. methanol, ethanol, or tert.butanol), or lower carboxylic acids (formic, glacial acetic, or propionic acid), or in aprotic organic solvents such as ethers (e.g. tetrahydrofuran, dioxan, or diethyl ether), liquid amides (e.g. dimethylformamide or hexamethylphosphordiamide), dimethylsulfoxide, or hydrocarbons (e.g. toluene or benzene), or mixtures of such solvents.
When carrying out the reaction under base catalyzed conditions, the catalyst may be selected from sodium, lithium, potassium, barium, calcium, magnesium, aluminum, ammonium, or quaternary ammonium hydroxides, lower alkoxides (e.g. methoxides, ethoxides, tert.butoxides), carbonates, borates, oxides, hydrides, or amides of lower secondary amines (e.g. diisopropyl amides or methylphenyl amides). Primary aromatic amines such as aniline, free secondary amines such as dimethyl amine, diethyl amine, piperidine, or pyrrolidine as well as basic ion exchange resins may also be used.
Acid catalysts may be selected from hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, sulfonic acids (such as paratoluenesulfonic or methanesulfonic acid), lower carboxylic acids (such as formic, acetic or propionic acid), lower halogenated carboxylic acids (such as trifluoroacetic acid), Lewis acids (such as BF3, POCl3, PCl5, or FeCl3), or acid ion exchange resins.
The reaction may be carried out at temperatures in the range of 0-100xc2x0 C., typically at room temperature. Reaction times may be from 30 min to 24 hours.
In another process b), compounds of the formula I in which W is xe2x80x94Cxe2x89xa1Cxe2x80x94 may be prepared by reacting an activated derivative of a carboxylic acid of the general formula
Xxe2x80x94Ar1xe2x80x94COOH
wherein X and Ar1 are as defined above, with an ethyne derivative of the formula IIxe2x80x2
Hxe2x80x94Cxe2x89xa1Cxe2x80x94Ar2xe2x80x94Yxe2x80x83xe2x80x83IIxe2x80x2
wherein Ar2 and Y are as defined above. Reactions of this type are described by Tohda, Y., Sonogashihara, K., Haghara, N., Synthesis 1977, p777-778. It is contemplated that the activated derivative of the carboxylic acid IV may be an activated ester, an anhydride or, preferably, an acid halogenide, in particular the acid chloride. The reaction is normally carried out using the catalysts described by Tohda, Y. et al. cited above, namely copper(I)iodide/triphenylphosphine-palladium dichloride.
The reaction is suitably carried out in triethylamine, a mixture of triethylamine and pyridine or triethylamine and toluene under a dry inert atmosphere such as nitrogen or argon.
The reaction is generally carried out at reduced temperature such as in the range from xe2x88x9280xc2x0 C. to room temperature, the reaction time typically being from 30 minutes to 6 hours.
In the above reactions, it may be preferred or necessary to protect various sensitive or reactive groups present in the starting compounds of formulas II, III, IV, or V so as to prevent said groups from interfering with the reactions. Such protection may be carried out in a well-known manner, e.g. as described in xe2x80x9cProtective Groups in Organic Chemistryxe2x80x9d by Theodora Green. For example, in the reaction between the acid derivative IV and the acetylene derivative V, a hydroxy group on Ar1 and/or Ar2 may be protected in the form of the methoxymethyl ether, N,N-diethylcarbamoyl ester, or allyl ether. The protecting group may be removed after the reaction in a manner known per se.
An alternative route for the preparation of the compounds of the general formula I goes via the 1,3-dipolar cycloaddition mechanism (Torssell, K. B. G., Nitrile oxides, Nitrones and nitronates in organic synthesis. Novel Strategies in Synthesis. VHC Verlagsgesellschaft, Weinheim 1988) known as the isoxazoline route.
Thus, by reaction of an aldehyde of the general formula A
Xxe2x80x94Ar1xe2x80x94CHOxe2x80x83xe2x80x83A
wherein X and Ar1 are as defined above, with hydroxylamine (e.g. hydroxylaminehydrochloride) using water as a solvent, the corresponding oxime of the general formula B
Xxe2x80x94Ar1xe2x80x94CHxe2x95x90Nxe2x80x94OHxe2x80x83xe2x80x83B
is formed, and a chlorinating agent (e.g. NCS or t-butylhypochlorite) is added to chlorinate the oxime, which in contact with alkenes of the general formula C
CHRxe2x95x90CRxe2x80x94Ar2xe2x80x94Yxe2x80x83xe2x80x83C
in which Ar2, Y and R are as defined above, will form the corresponding isoxazoline of the formula D 
The chlorination and the formation of the isoxazoline ring can be performed by a one-pot method. Solvents like methylenechloride, chloroform are most commonly used. By reducing the formed isoxazoline in an aqueous medium, the reduced product will be hydrolyzed to a xcex2-hydroxyketone of the general formula E,
Xxe2x80x94Ar1COxe2x80x94CRHxe2x80x94C(OH)Rxe2x80x94Ar2xe2x80x94Yxe2x80x83xe2x80x83E
wherein Ar1, Ar2, X and Y are as defined above. This reduction, including the hydrolysis, is a very efficient synthetic tool, and gives products in almost 100% yield. The reduction can be carried out by the use of Raxe2x80x94Ni together with catalytic amounts of acid or by electrochemical reduction. Optionally, the hydroxy group is substituted with another leaving group such as halide, alkoxy, tosyloxy, or trifluoromethanesulfonoxy, such other leaving group being introduced in a manner known per se. When the hydroxy group is not substituted with such other leaving group, this xcex2-hydroxy-ketone (E) is treated with acid (e.g. paratoluenesulfonic acid or a mixture of acetic acid and sodium acetate), whereby water is eliminated, giving the chalcone structure of the general formula (I).
Correspondingly, compounds in which W is xe2x80x94Cxe2x89xa1Cxe2x80x94 can be made via a route where the oxime of the above general formula B is reacted with a halogenating agent and an acetylene of the general formula C1
CHxe2x89xa1Cxe2x80x94Ar2xe2x80x94Yxe2x80x83xe2x80x83C1
wherein Ar2 is as defined above, is added to form the corresponding isoxazole of the formula D1 
wherein Ar1, Ar2, X and Y are as defined above, which is then reduced, and the reduction product is hydrolysed to form a xcex2-hydroxyketone of the general formula E1
Xxe2x80x94Ar1xe2x80x94CHxe2x95x90C(OH)xe2x80x94Ar2xe2x80x94Yxe2x80x83xe2x80x83E1
wherein Ar1, Ar2, X and Y are as defined above, and optionally substituting the hydroxy group with another leaving group such as halide, alkoxy, tosyloxy, or trifluoromethanesulfonoxy, such other leaving group being introduced in a manner known per se. By elimination of the leaving group, the compound of the general formula I, wherein W is xe2x80x94Cxe2x89xa1Cxe2x80x94, is obtained.
Another route for the preparation of the compounds of the general formula I Is the Wittig reaction in which an aldehyde of the general formula F
Yxe2x80x94Ar2xe2x80x94CHOxe2x80x83xe2x80x83F
wherein Ar2 and Y are as defined above, is treated with a phosphorus ylide (also called a phosphorane) of the general formula G,
T3xe2x80x94Pxe2x95x90CHxe2x80x94COxe2x80x94Ar1xe2x80x94Xxe2x80x83xe2x80x83G
in which T can be aliphatic, alicyclic or aromatic, to give the chalcone structure of the general formula (I). The Wittig reaction is known as an exceedingly useful method for the synthesis of alkenes.
The aldehyde may be aliphatic, alicyclic or aromatic; it may contain double or triple bonds; it may contain various functional groups, such as OH, OR, NR2, aromatic nitro or halo, acetal or even ester groups. Double or triple bonds conjugated with the carbonyl also do not interfere; the attack is directed towards the carbonyl carbon atom.
The reaction is suitably carried out in aprotic organic solvents such as ethers (e.g. tetrahydrofuran, dioxan, or diethyl ether) or DMSO or mixtures of these.
The reaction is normally carried out at temperatures in the range of 0-25xc2x0 C., but can also be carried out at even lower temperatures.
Phosphoranes of the general formula MenPh(3xe2x88x92n)Pxe2x95x90CHCOPh (Ph=phenyl or substituted phenyl, n=0,1,2,3) are reported to react with benzaldehyde to give chalcone in good yield (70-90%). According to DE 1.256.642 (1967), the Wittig reaction is used for the preparation of chalcone in 84% yield (Bestmann, H. J., and Kratzer, O.).
Another route for the preparation of compounds of the general formula I is by reacting benzaldehyde with N-xcex1-styrylmorpholine (Birkofer, L., Kim, S. M., and Engels, H. D., Chem. Ber., 95, 1495 (1962)).
A styrene compound of the general formula H
Xxe2x80x94Ar1CVxe2x95x90CH2xe2x80x83xe2x80x83H
in which V represents a secondary amino group, is reacted with an aldehyde of the general formula J
xe2x80x83Yxe2x80x94Ar2xe2x80x94CHOxe2x80x83xe2x80x83J
to form an intermediate which after hydrolysis and elimination of the secondary amino group gives a compound of the structure K 
wherein X, Y, Ar1, Ar2 and R are as defined above. In the compound K, the hydroxy group may, if desired, be substituted with another leaving group such as alkoxy, tosyloxy, trifluoromethanesulfonoxy or acyloxy in a manner known per se. After elimination of HOH or HOTt, wherein Tt is such other leaving group, the chalcone structure of the general structure (I) is obtained.
The usefulness of enamines as intermediates lies in the fact that the xcex2-carbon of the double bond of the enamine has nucleophilic character. This will make the reaction between the enamine and the aldehyde possible.
Another route for the synthesis of compounds of the general formula I is by reacting derivatives of cinnamic acid which is based on the fact that cinnamic acid can react with aromatic compounds (e.g. phenols and benzene).
Cinnamic acids of the general formula L
Yxe2x80x94Ar2xe2x80x94CHxe2x95x90CHxe2x80x94COQxe2x80x83xe2x80x83L
in which Q is either a hydroxy group, a carboxylate or a halogen, are condensed with aromates of the general formula M
Xxe2x80x94Ar1xe2x80x83xe2x80x83M
to give xcex1,xcex2-unsaturated ketones of the general formula (I).
The reaction is best carried out in the presence of BF3 (Starkova, S. P., Starkova, S. P., and Goncharenko, G. A., Izv. Vyssh. Ucheb. Zaved., Khim. Khim. Tekhnol., 20, 1149 (1977); Chem. Abstr., 88, 22272j (1978)) or polyphosphoric acid (Reichel, L., and Proksch, G., Justus Liebigs Ann. Chem., 745, 59 (1971)). With the former agent, a high preference for para-acylation is observed.
The reaction is preferably carried out in the presence of AlCl3 as a catalyst (Rasschaert, A., Janssens, W., and Slootmaekers, P. J., Bull. Soc. Chim. Belges., 75, 449 (1966); Chem. Abstr., 66,2305e (1967)).
The two latter methods are examples of the Friedel-Craft acylation. Among the reagents (compounds L) used are not only acyl halides or the adds, but also anhydrides.
The reaction can be carried out with only very small amounts of catalyst, often just a trace and sometimes without any catalyst at all. Ferric chloride, iodine, zinc chloride, and iron are the most common catalysts used. Proton acids can be used as catalyst when the reagent (compound L) is in its acid form.
In order to prevent acylation of the solvent used, the reaction is often carried out in a non-aromatic fully saturated solvent or in an aromatic solvent with deactivating groups, which prevents acylation, such as, for example, nitrobenzene.
The reaction is carried out at wide varying temperatures depending on the nature of the reacting compounds.
The prodrugs of the general formula I can be made directly by processes as described below, the desired prodrug groups being in place in the relevant reagents in question, or free AZ groups in which Z is hydrogen, in particular hydroxy groups, can be converted to the corresponding groups in which Z is one of the groups (A) to (E) as defined above.
(Acyloxy)alkyl-xcex1-ethers such as those of the general formulas (IIDa, IIEa, IIEb, Ixe2x80x2Db, Ixe2x80x2Eb, IIIDa, IIIEa) can be prepared by reacting the corresponding phenols of the general formulas (IIa, IIb, IIIa) with the appropriate (acyloxy)alkyl-xcex1-halide. slettes?
The reaction is most often carried out using acetone or butanone as solvents.
A weak base like potassium carbonate may be added as an acid scavenger.
In the case of pivaloyloxymethyl-xcex1-halides, the halogen should be iodine in order to avoid formation of pivalic esters of phenol (Sloan, K. B., and Koch, S. A. M., J. Org. Chem. 48 (1983) 3777-3783.)
Carboxylic esters of the phenols of the general formula I (Ixe2x80x2Ab, IIAa, IIIAa) may be prepared by reacting the corresponding phenols (e.g. IIa, IIb, IIIa) with an activated ester (including the xcex1-halomethylesters), an anhydride or, preferably, an acid halogenide, in particular the acid chloride.
The reaction is performed in an aprotic organic solvent such as lower aliphatic ketones like acetone, butanone, aliphatic ethers like tetrahydrofuran, diethylether, or dioxane or a liquid amine like pyridine.
The reaction is carried out in the presence of an acid scavenger such as potassium or sodium carbonate, an tertiary aliphatic amine such as triethylamine, or pyridine.
An especially spectacular modification of the method involves the reaction of the phenol with the appropriate anhydride using 4-dimethylaminopyridine or 4-(1-pyrrolidino)pyridine as catalyst. With these reaction conditions, the reaction gives a very high yield.
N,N-Dimethylcarbamic esters of the phenols of the general formula I (Ixe2x80x2Bb, IIIBa) may be prepared by reacting the corresponding phenols of the general formula I (IIa, IIb) with an activated derivative of N,N-dimethylcarbamic acid such as an activated ester or, preferably, an acid halide, in particular the acid chloride.
The reaction is carried out in an aprotic organic solvent such as lower aliphatic ketones like acetone, butanone, aliphatic ethers such as tetrahydrofuran, diethylether, or dioxane, or a liquid amine such as pyridine, or a liquid nitrile such as acetonitrile.
In general, the reaction is carried out in the presence of an acid scavenger such as potassium or sodium carbonate, a tertiary aliphatic amine such as triethylamine or pyridine.
Alternatively, the N,N-dimethylcarbamoyl esters may be prepared by condensing the carbamoylated phenolic benzaldehydes or phenolic acetophenones with the appropriate acetophenones or benzaldehydes, respectively.
The alkoxymethoxy ethers of the general formula I (Ixe2x80x2Cb, IICa, IICb, IIICa) are most conveniently prepared by condensing the appropriate ethers of the phenolic benzaldehydes or the phenolic acetophenones with the appropriate acetophenones or benzaldehydes, respectively.
They may, however, be prepared by reacting the phenolic chalcones with the appropriate alkyl-xcex1-alkylhalomethyl halide.
The reaction may be carried out in an aprotic organic solvent like a lower aliphatic ketone, such as acetone or butanone, or an ether, such as tetrahydrofuran, dioxane or dioxolane or a liquid nitrile such as acetonitrile.
The reaction may be performed in the presence of a acid scavenger such as an inorganic or organic base. The base may be potassium or sodium or quaternary ammonium carbonate, or hydroxide.